VICTOZA is indicated:

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infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease.

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Limitations of Use:

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VICTOZA contains liraglutide. Coadministration with other liraglutide-containing products is not recommended.

{ "type": "p", "children": [], "text": "\nVICTOZA contains liraglutide. Coadministration with other liraglutide-containing products is not recommended." }

Adult Patients

Pediatric Patients Aged 10 Years and Older

Injection: 18 mg/3 mL (6 mg/mL) clear, colorless solution in a pre-filled, single-patient-use pen that delivers doses of 0.6 mg, 1.2 mg, or 1.8 mg.

{ "type": "p", "children": [], "text": "Injection: 18 mg/3 mL (6 mg/mL) clear, colorless solution in a pre-filled, single-patient-use pen that delivers doses of 0.6 mg, 1.2 mg, or 1.8 mg." }

VICTOZA is contraindicated in patients with a:

{ "type": "p", "children": [], "text": "VICTOZA is contraindicated in patients with a: " }

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Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors (adenomas and/or carcinomas) at clinically relevant exposures in both genders of rats and mice [see Nonclinical Toxicology (13.1)]. Malignant thyroid C-cell carcinomas were detected in rats and mice. It is unknown whether VICTOZA will cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.

Cases of MTC in patients treated with VICTOZA have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and VICTOZA use in humans.

VICTOZA is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of VICTOZA and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness).

Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with VICTOZA. Such monitoring may increase the risk of unnecessary procedures, due to low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin may indicate MTC and patients with MTC usually have calcitonin values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.

Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in

patients treated with glucagon-like peptide-1 (GLP-1) receptor agonists, including VICTOZA [see Adverse Reactions (6)]. After initiation of VICTOZA, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue VICTOZA and initiate appropriate management.

VICTOZA pens must never be shared between patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens.

Adult patients receiving VICTOZA in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. In pediatric patients 10 years of age and older, the risk of hypoglycemia was higher with VICTOZA regardless of insulin and/or metformin use. [see Adverse Reactions (6.1), Drug Interactions (7.2)].

The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin. Inform patients using these concomitant medications and pediatric patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.

There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with VICTOZA [see Adverse Reactions (6.2)]. The majority of the reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea [see Adverse Reactions (6.1)]. Monitor renal function in patients reporting adverse reactions to VICTOZA that could lead to volume depletion, especially during dosage initiation and escalation of VICTOZA.[see Use in Specific Populations (8.6)].

Use of GLP-1 receptor agonists, including VICTOZA, has been associated with gastrointestinal adverse reactions, sometimes severe [see Adverse Reactions (6)]. In VICTOZA clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving VICTOZA (1.2 mg 4.4 %, 1.8 mg 4.2 %) than placebo (1.1 %). VICTOZA is not recommended in patients with severe gastroparesis.

There have been postmarketing reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema) in patients treated with VICTOZA [see Adverse Reactions (6.2)]. If a hypersensitivity reaction occurs, discontinue VICTOZA; treat promptly per standard of care, and monitor until signs and symptoms resolve.

Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists. Use caution in a patient with a history of anaphylaxis or angioedema with another GLP-receptor agonist because it is unknown whether such patients will be predisposed to these reactions with VICTOZA. VICTOZA is contraindicated in patients who have had a serious hypersensitivity reaction to liraglutide or any of the excipients in VICTOZA [see Contraindications (4)].

Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In the LEADER trial [see Clinical Studies (14.3)], 3.1% of VICTOZA-treated patients versus 1.9% of placebo-treated patients reported an acute event of gallbladder disease, such as cholelithiasis or cholecystitis [see Adverse Reactions (6.1)]. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.

VICTOZA delays gastric emptying [see Clinical Pharmacology (12.2)]. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations.

Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking VICTOZA, including whether modifying preoperative fasting recommendations or temporarily discontinuing VICTOZA could reduce the incidence of retained gastric contents. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking VICTOZA.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Common Adverse Reactions

The safety of VICTOZA in patients with type 2 diabetes mellitus was evaluated in 5 glycemic control, placebo-controlled trials in adults and one trial of 52 weeks duration in pediatric patients 10 years of age and older [see Clinical Studies (14.1)]. The data in Table 1 reflect exposure of 1,673 adult patients to VICTOZA and a mean duration of exposure to VICTOZA of 37.3 weeks. The mean age of adult patients was 58 years, 4% were 75 years or older and 54% were male. The population was 79% White, 6% Black or African American, 13% Asian; 4% were of Hispanic or Latino ethnicity. At baseline the population had diabetes for an average of 9 years and a mean HbA1c of 8.4%. Baseline estimated renal function was normal or mildly impaired in 88% and moderately impaired in 12% of the pooled population.

Table 1 shows common adverse reactions in adults, excluding hypoglycemia, associated with the use of VICTOZA for the treatment of type 2 diabetes mellitus. These adverse reactions occurred more commonly on VICTOZA than on placebo and occurred in at least 5% of patients treated with VICTOZA. Overall, the type, and severity of adverse reactions in pediatric patients 10 years of age and older and above were comparable to that observed in the adult population.

Table 1. Adverse reactions reported in ≥ 5% of Adult Patients Treated with VICTOZA for Type 2 Diabetes Mellitus

<div class="scrollingtable"><table width="100%"> <col width="32%"/> <col width="19%"/> <col width="19%"/> <col width="19%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="middle"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">N=661</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Liraglutide 1.2 mg</span> </p> <p> <span class="Bold">N= 645</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Liraglutide 1.8 mg</span> </p> <p> <span class="Bold">N= 1024</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Adverse Reaction </span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Nausea </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">18</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">20</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Diarrhea </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">10</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Headache </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">11</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">10</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Nasopharyngitis</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">10</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Vomiting </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">6</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Decreased appetite</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">10</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Dyspepsia</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Upper Respiratory Tract Infection</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">6</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Constipation </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Back Pain</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5</p> </td> </tr> </tbody> </table></div>

Cumulative proportions were calculated combining studies using Cochran-Mantel-Haenszel weights.

In an analysis of placebo- and active-controlled trials, the types and frequency of common adverse reactions, excluding hypoglycemia, were similar to those listed in Table 1.

Other Adverse Reactions

Gastrointestinal Adverse Reactions

In the pool of 5 glycemic control, placebo-controlled adult clinical trials, withdrawals due to gastrointestinal adverse reactions, occurred in 4.3% of VICTOZA-treated patients and 0.5% of placebo-treated patients. Severe gastrointestinal adverse reactions were reported more frequently among patients receiving VICTOZA (1.2 mg 4.4 %, 1.8 mg 4.2 %) than placebo (1.1 %). Withdrawal due to gastrointestinal adverse events mainly occurred during the first 2-3 months of the trials.

Injection site reactions

Injection site reactions (e.g., injection site rash, erythema) were reported in approximately 2% of VICTOZA-treated adult patients in the five double-blind, glycemic control trials of at least 26 weeks duration. Less than 0.2% of VICTOZA-treated patients discontinued due to injection site reactions.

Hypoglycemia

In 5 adult glycemic control, placebo-controlled clinical trials of at least 26 weeks duration, hypoglycemia requiring the assistance of another person for treatment occurred in 8 VICTOZA-treated patients (7.5 events per 1000 patient-years). Of these 8 VICTOZA-treated patients, 7 patients were concomitantly using a sulfonylurea.

<div class="scrollingtable"><table width="425.4pt"> <caption> <span>Table 2. Adult Incidence (%) and Rate (episodes/patient year) of Hypoglycemia in 26-Week Combination Therapy Placebo-controlled Trials</span> </caption> <col width="31%"/> <col width="29%"/> <col width="29%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">Placebo Comparator</span> </dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">VICTOZA Treatment</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Add-on to </span> </p> <p> <span class="Bold">Metformin</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Placebo + Metformin</span> </p> <p>(N = 121)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">VICTOZA + Metformin</span> </p> <dl> <dt> </dt> <dd>(N = 724)</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patient not able to self-treat </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>0</dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>0.1 (0.001)</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patient able to self-treat</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>2.5 (0.06)</dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>3.6 (0.05)</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Add-on to </span> </p> <p> <span class="Bold">Glimepiride</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">Placebo + Glimepiride</span> </dd> <dt> </dt> <dd>(N = 114)</dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">VICTOZA + Glimepiride</span> </dd> <dt> </dt> <dd>(N = 695)</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patient not able to self-treat </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>0</dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>0.1 (0.003)</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patient able to self-treat</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>2.6 (0.17)</dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>7.5 (0.38)</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Not classified</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>0</dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>0.9 (0.05)</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Add-on to </span> </p> <p> <span class="Bold">Metformin + Rosiglitazone</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <dl> <dt> </dt> <dd> <span class="Bold">Placebo + Metformin + Rosiglitazone</span> </dd> </dl> <p class="First">(N = 175)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">VICTOZA + Metformin +</span> </p> <p> <span class="Bold">Rosiglitazone</span> </p> <dl> <dt> </dt> <dd>(N = 355)</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patient not able to self-treat </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>0</dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>0</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patient able to self-treat</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>4.6 (0.15)</dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>7.9 (0.49)</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Not classified</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>1.1 (0.03)</dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>0.6 (0.01)</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Add-on to </span> </p> <p> <span class="Bold">Metformin + Glimepiride</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">Placebo + Metformin + </span> </dd> <dt> </dt> <dd> <span class="Bold">Glimepiride</span> </dd> </dl> <p class="First">(N = 114)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">VICTOZA + Metformin +</span> </p> <p> <span class="Bold">Glimepiride</span> </p> <dl> <dt> </dt> <dd>(N = 230)</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patient not able to self-treat </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>0</dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>2.2 (0.06)</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Patient able to self-treat</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>16.7 (0.95)</dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>27.4 (1.16)</dd> </dl> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Not classified</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>0</dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>0</dd> </dl> </td> </tr> </tbody> </table></div>

“Patient not able to self-treat” is defined as an event requiring the assistance of another person for treatment.

In a 26-week placebo-controlled clinical trial in pediatric patients 10 years of age and older with a 26-week open-label extension, 21.2% of VICTOZA-treated patients (mean age 14.6 years) with type 2 diabetes mellitus, had hypoglycemia with a blood glucose <54 mg/dL with or without symptoms (335 events per 1000 patient years). No severe hypoglycemic episodes occurred in the VICTOZA treatment group (severe hypoglycemia was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions).

Papillary thyroid carcinoma

In adult glycemic control trials of VICTOZA, there were 7 reported cases of papillary thyroid carcinoma in patients treated with VICTOZA and 1 case in a comparator-treated patient (1.5 vs. 0.5 cases per 1000 patient-years). Most of these papillary thyroid carcinomas were <1 cm in greatest diameter and were diagnosed in surgical pathology specimens after thyroidectomy prompted by findings on protocol-specified screening with serum calcitonin or thyroid ultrasound.

Pancreatitis

In glycemic control trials of VICTOZA, there have been 13 cases of pancreatitis among VICTOZA-treated patients and 1 case in a comparator (glimepiride) treated patient (2.7 vs. 0.5 cases per 1000 patient-years). Nine of the 13 cases with VICTOZA were reported as acute pancreatitis and four were reported as chronic pancreatitis. In one case in a VICTOZA-treated patient, pancreatitis, with necrosis, was observed and led to death; however clinical causality could not be established. Some patients had other risk factors for pancreatitis, such as a history of cholelithiasis or alcohol abuse.

Cholelithiasis and cholecystitis

In adult glycemic control trials of VICTOZA, the incidence of cholelithiasis was 0.3% in both VICTOZA-treated and placebo-treated patients. The incidence of cholecystitis was 0.2% in both VICTOZA-treated and placebo-treated patients.

In the LEADER trial [see Clinical Studies (14.3)], the incidence of cholelithiasis was 1.5% (3.9 cases per 1000 patient years of observation) in adult VICTOZA-treated and 1.1% (2.8 cases per 1000 patient years of observation) in placebo-treated patients, both on a background of standard of care. The incidence of acute cholecystitis was 1.1% (2.9 cases per 1000 patient years of observation) in adult VICTOZA-treated and 0.7% (1.9 cases per 1000 patient years of observation) in placebo-treated patients. The majority of events required hospitalization or cholecystectomy.

Laboratory Tests

Bilirubin

In the five adult glycemic control trials of at least 26 weeks duration, mildly elevated serum bilirubin concentrations (elevations to no more than twice the upper limit of the reference range) occurred in 4.0% of VICTOZA-treated patients, 2.1% of placebo-treated patients and 3.5% of active-comparator-treated patients. This finding was not accompanied by abnormalities in other liver tests. The significance of this isolated finding is unknown.

Calcitonin

Calcitonin, a biological marker of MTC, was measured throughout the clinical development program. At the end of the adult glycemic control trials, adjusted mean serum calcitonin concentrations were higher in VICTOZA-treated patients compared to placebo-treated patients but not compared to patients receiving active comparator. Between group differences in adjusted mean serum calcitonin values were approximately 0.1 ng/L or less. Among adult patients with pretreatment calcitonin <20 ng/L, calcitonin elevations to >20 ng/L occurred in 0.7% of VICTOZA-treated patients, 0.3% of placebo-treated patients, and 0.5% of active-comparator-treated patients. The clinical significance of these findings is unknown.

Lipase and Amylase

In one adult glycemic control trial in renal impairment patients, a mean increase of 33% for lipase and 15% for amylase from baseline was observed for VICTOZA-treated patients while placebo-treated patients had a mean decrease in lipase of 3% and a mean increase in amylase of 1%.

In the LEADER trial, serum lipase and amylase were routinely measured. Among adult VICTOZA-treated patients, 7.9% had a lipase value at any time during treatment of greater than or equal to 3 times the upper limit of normal compared with 4.5% of placebo-treated patients, and 1% of VICTOZA-treated patients had an amylase value at any time during treatment of greater than or equal to 3 times the upper limit of normal versus 0.7% of placebo-treated patients.

The clinical significance of elevations in lipase or amylase with VICTOZA is unknown in the absence of other signs and symptoms of pancreatitis [see Warnings and Precautions (5.2)].

Vital signs

VICTOZA did not have adverse effects on blood pressure. Mean increases from baseline in heart rate of 2 to 3 beats per minute have been observed in adult patients treated with VICTOZA compared to placebo.

The following additional adverse reactions have been reported during post-approval use of VICTOZA. Because these events are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

VICTOZA causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, VICTOZA did not affect the absorption of the tested orally administered medications to any clinically relevant degree [see Clinical Pharmacology (12.3)]. Nonetheless, caution should be exercised when oral medications are concomitantly administered with VICTOZA.

VICTOZA stimulates insulin release in the presence of elevated blood glucose concentrations. Patients receiving VICTOZA in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. When initiating VICTOZA, consider reducing the dose of concomitantly administered insulin secretagogues (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)].

Risk Summary

Based on animal reproduction studies, there may be risks to the fetus from exposure to VICTOZA during pregnancy. VICTOZA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Animal reproduction studies identified increased adverse developmental outcomes from exposure during pregnancy. Liraglutide exposure was associated with early embryonic deaths and an imbalance in some fetal abnormalities in pregnant rats administered liraglutide during organogenesis at doses that approximate clinical exposures at the maximum recommended human dose (MRHD) of 1.8 mg/day. In pregnant rabbits administered liraglutide during organogenesis, decreased fetal weight and an increased incidence of major fetal abnormalities were seen at exposures below the human exposures at the MRHD [see Animal Data].

The estimated background risk of major birth defects for women with uncontrolled pre-gestational diabetes (Hemoglobin A1C >7) is 6 to 10%. The major birth defect rate has been reported to be as high as 20 to 25% in women with a Hemoglobin A1C >10. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity.

Animal Data

Female rats given subcutaneous doses of 0.1, 0.25 and 1.0 mg/kg/day liraglutide beginning 2 weeks before mating through gestation day 17 had estimated systemic exposures 0.8-, 3-, and 11-times the human exposure at the MRHD based on plasma AUC comparison. The number of early embryonic deaths in the 1 mg/kg/day group increased slightly. Fetal abnormalities and variations in kidneys and blood vessels, irregular ossification of the skull, and a more complete state of ossification occurred at all doses. Mottled liver and minimally kinked ribs occurred at the highest dose. The incidence of fetal malformations in liraglutide-treated groups exceeding concurrent and historical controls were misshapen oropharynx and/or narrowed opening into larynx at 0.1 mg/kg/day and umbilical hernia at 0.1 and 0.25 mg/kg/day.

Pregnant rabbits given subcutaneous doses of 0.01, 0.025 and 0.05 mg/kg/day liraglutide from gestation day 6 through day 18 inclusive, had estimated systemic exposures less than the human exposure at the MRHD of 1.8 mg/day at all doses, based on plasma AUC. Liraglutide decreased fetal weight and dose-dependently increased the incidence of total major fetal abnormalities at all doses. The incidence of malformations exceeded concurrent and historical controls at 0.01 mg/kg/day (kidneys, scapula), ≥ 0.01 mg/kg/day (eyes, forelimb), 0.025 mg/kg/day (brain, tail and sacral vertebrae, major blood vessels and heart, umbilicus), ≥ 0.025 mg/kg/day (sternum) and at 0.05 mg/kg/day (parietal bones, major blood vessels). Irregular ossification and/or skeletal abnormalities occurred in the skull and jaw, vertebrae and ribs, sternum, pelvis, tail, and scapula; and dose-dependent minor skeletal variations were observed. Visceral abnormalities occurred in blood vessels, lung, liver, and esophagus. Bilobed or bifurcated gallbladder was seen in all treatment groups, but not in the control group.

In pregnant female rats given subcutaneous doses of 0.1, 0.25 and 1.0 mg/kg/day liraglutide from gestation day 6 through weaning or termination of nursing on lactation day 24, estimated systemic exposures were 0.8-, 3-, and 11-times human exposure at the MRHD of 1.8 mg/day, based on plasma AUC. A slight delay in parturition was observed in the majority of treated rats. Group mean body weight of neonatal rats from liraglutide-treated dams was lower than neonatal rats from control group dams. Bloody scabs and agitated behavior occurred in male rats descended from dams treated with 1 mg/kg/day liraglutide. Group mean body weight from birth to postpartum day 14 trended lower in F2 generation rats descended from liraglutide-treated rats compared to F2 generation rats descended from controls, but differences did not reach statistical significance for any group.

Risk Summary

There are no data on the presence of VICTOZA in human milk, the effects on the breastfed infant, or the effects on milk production. Liraglutide was present in milk of lactating rats [see Data].

Developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VICTOZA and any potential adverse effects on the breastfed infant from VICTOZA or from the underlying maternal condition.

Data

In lactating rats, liraglutide was present unchanged in milk at concentrations approximately 50% of maternal plasma concentrations.

The safety and effectiveness of VICTOZA as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus have been established in pediatric patients 10 years of age and older. Use of VICTOZA for this indication is supported by a 26-week placebo-controlled clinical trial and a 26-week open-label extension in 134 pediatric patients 10 to 17 years of age with type 2 diabetes mellitus, a pediatric pharmacokinetic study, and studies in adults with type 2 diabetes mellitus [see Clinical Pharmacology (12.3) and Clinical Studies (14.1,14.2)]. The risk of hypoglycemia was higher with VICTOZA in pediatric patients regardless of insulin and/or metformin use [see Adverse Reactions (6.1)].

The safety and effectiveness of VICTOZA have not been established in pediatric patients less than 10 years of age.

In the VICTOZA treatment arms of the glycemic control trials, a total of 832 (19.3%) of the patients were 65 to 74 years of age and 145 (3.4%) were 75 years of age and over [see Clinical Studies (14.1)]. In the VICTOZA treatment arm of the LEADER trial [see Clinical Studies (14.3)], a total of 1738 (37.2%) patients were 65 to 74 years of age, 401 (8.6%) were 75 to 84 years of age, and 17 (0.4%) were 85 years of age or older at baseline.

No overall differences in safety or effectiveness for VICTOZA have been observed between patients 65 years of age and older and younger patients.

No dose adjustment of VICTOZA is recommended for patients with renal impairment [see Clinical Pharmacology (12.3)]. The safety and efficacy of VICTOZA was evaluated in a 26-week clinical study that included patients with moderate renal impairment (eGFR 30 to 60 mL/min/1.73m2) [see Clinical Studies (14.1)].

In the VICTOZA treatment arm of the LEADER trial [see Clinical Studies (14.3)], 1,932 (41.4%) patients had mild renal impairment, 999 (21.4%) patients had moderate renal impairment and 117 (2.5%) patients had severe renal impairment at baseline. No overall differences in safety or efficacy were seen in these patients compared to patients with normal renal function.

There is limited experience with VICTOZA in patients with end stage renal disease.

There is limited experience in patients with mild, moderate or severe hepatic impairment. Therefore, VICTOZA should be used with caution in this patient population. No dose adjustment of VICTOZA is recommended for patients with hepatic impairment [see Clinical Pharmacology (12.3)].

Overdoses have been reported in clinical trials and post-marketing use of VICTOZA. Observed effects have included severe nausea, severe vomiting, and severe hypoglycemia. In the event of overdosage, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Initiate appropriate supportive treatment according to the patient’s clinical signs and symptoms.

{ "type": "p", "children": [], "text": "Overdoses have been reported in clinical trials and post-marketing use of VICTOZA. Observed effects have included severe nausea, severe vomiting, and severe hypoglycemia. In the event of overdosage, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Initiate appropriate supportive treatment according to the patient’s clinical signs and symptoms." }

VICTOZA contains liraglutide, an analog of human GLP-1 and acts as a GLP-1 receptor agonist. The peptide precursor of liraglutide, produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae, has been engineered to be 97% homologous to native human GLP-1 by substituting arginine for lysine at position 34. Liraglutide is made by attaching a C-16 fatty acid (palmitic acid) with a glutamic acid spacer on the remaining lysine residue at position 26 of the peptide precursor. The molecular formula of liraglutide is C172H265N43O51 and the molecular weight is 3751.2 Daltons. The structural formula (Figure 1) is:

{ "type": "p", "children": [], "text": "VICTOZA contains liraglutide, an analog of human GLP-1 and acts as a GLP-1 receptor agonist. The peptide precursor of liraglutide, produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae, has been engineered to be 97% homologous to native human GLP-1 by substituting arginine for lysine at position 34. Liraglutide is made by attaching a C-16 fatty acid (palmitic acid) with a glutamic acid spacer on the remaining lysine residue at position 26 of the peptide precursor. The molecular formula of liraglutide is C172H265N43O51 and the molecular weight is 3751.2 Daltons. The structural formula (Figure 1) is:" }

Figure 1. Structural Formula of liraglutide

{ "type": "p", "children": [], "text": "\nFigure 1. Structural Formula of liraglutide\n" }

VICTOZA injection is a sterile, aqueous, clear, colorless or almost colorless solution for subcutaneous use. Each 1 mL of VICTOZA solution contains 6 mg of liraglutide and the following inactive ingredients: disodium phosphate dihydrate, 1.42 mg; propylene glycol, 14 mg; phenol, 5.5 mg; and water for injection. VICTOZA has a pH of approximately 8.15, hydrochloric acid or sodium hydroxide may be added to adjust pH. Each pre-filled pen contains a 3 mL solution of VICTOZA equivalent to 18 mg liraglutide (free-base, anhydrous).

{ "type": "p", "children": [], "text": "VICTOZA injection is a sterile, aqueous, clear, colorless or almost colorless solution for subcutaneous use. Each 1 mL of VICTOZA solution contains 6 mg of liraglutide and the following inactive ingredients: disodium phosphate dihydrate, 1.42 mg; propylene glycol, 14 mg; phenol, 5.5 mg; and water for injection. VICTOZA has a pH of approximately 8.15, hydrochloric acid or sodium hydroxide may be added to adjust pH. Each pre-filled pen contains a 3 mL solution of VICTOZA equivalent to 18 mg liraglutide (free-base, anhydrous)." }

Liraglutide is an acylated human GLP-1 receptor agonist with 97% amino acid sequence homology to endogenous human GLP-1(7-37). GLP-1(7-37) represents <20% of total circulating endogenous GLP-1. Like GLP-1(7-37), liraglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase by the stimulatory G-protein, Gs, in pancreatic beta cells. Liraglutide increases intracellular cyclic AMP (cAMP) leading to insulin release in the presence of elevated glucose concentrations. This insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia. Liraglutide also decreases glucagon secretion in a glucose-dependent manner. The mechanism of blood glucose lowering also involves a delay in gastric emptying.

GLP-1(7-37) has a half-life of 1.5-2 minutes due to degradation by the ubiquitous endogenous enzymes, dipeptidyl peptidase 4 (DPP-4) and neutral endopeptidases (NEP). Unlike native GLP-1, liraglutide is stable against metabolic degradation by both peptidases and has a plasma half-life of 13 hours after subcutaneous administration. The pharmacokinetic profile of liraglutide, which makes it suitable for once daily administration, is a result of self-association that delays absorption, plasma protein binding and stability against metabolic degradation by DPP-4 and NEP.

VICTOZA’s pharmacodynamic profile is consistent with its pharmacokinetic profile observed after single subcutaneous administration as VICTOZA lowered fasting, premeal and postprandial glucose throughout the day [see Clinical Pharmacology (12.3)].

Fasting and postprandial glucose was measured before and up to 5 hours after a standardized meal after treatment to steady state with 0.6, 1.2 and 1.8 mg VICTOZA or placebo. Compared to placebo, the postprandial plasma glucose AUC0-300min was 35% lower after VICTOZA 1.2 mg and 38% lower after VICTOZA 1.8 mg.

Glucose-dependent insulin secretion

The effect of a single dose of 7.5 mcg/kg (~ 0.7 mg) VICTOZA on insulin secretion rates (ISR) was investigated in 10 patients with type 2 diabetes mellitus during graded glucose infusion. In these patients, on average, the ISR response was increased in a glucose-dependent manner (Figure 2).

Figure 2. Mean Insulin Secretion Rate (ISR) versus Glucose Concentration Following Single-Dose VICTOZA 7.5 mcg/kg (~ 0.7 mg) or Placebo in Patients with Type 2 Diabetes Mellitus (N=10) During Graded Glucose Infusion

Glucagon secretion

VICTOZA lowered blood glucose by stimulating insulin secretion and lowering glucagon secretion. A single dose of VICTOZA 7.5 mcg/kg (~ 0.7 mg) did not impair glucagon response to low glucose concentrations.

Gastric emptying

VICTOZA causes a delay of gastric emptying, thereby reducing the rate at which postprandial glucose appears in the circulation.

Cardiac Electrophysiology (QTc)

The effect of VICTOZA on cardiac repolarization was tested in a QTc study. VICTOZA at steady state concentrations with daily doses up to 1.8 mg did not produce QTc prolongation.

Absorption

Following subcutaneous administration, maximum concentrations of liraglutide are achieved at 8-12 hours post dosing. The mean peak (Cmax) and total (AUC) exposures of liraglutide were 35 ng/mL and 960 ng·h/mL, respectively, for a subcutaneous single dose of 0.6 mg. After subcutaneous single dose administrations, Cmax and AUC of liraglutide increased proportionally over the therapeutic dose range of 0.6 mg to 1.8 mg. At 1.8 mg VICTOZA, the average steady state concentration of liraglutide over 24 hours was approximately 128 ng/mL. AUC0-∞ was equivalent between upper arm and abdomen, and between upper arm and thigh. AUC0-∞ from thigh was 22% lower than that from abdomen. However, liraglutide exposures were considered comparable among these three subcutaneous injection sites. Absolute bioavailability of liraglutide following subcutaneous administration is approximately 55%.

Distribution

The mean apparent volume of distribution after subcutaneous administration of VICTOZA 0.6 mg is approximately 13 L. The mean volume of distribution after intravenous administration of VICTOZA is 0.07 L/kg. Liraglutide is extensively bound to plasma protein (>98%).

Elimination

The mean apparent clearance following subcutaneous administration of a single dose of liraglutide is approximately 1.2 L/h with an elimination half-life of approximately 13 hours.

Metabolism

During the initial 24 hours following administration of a single [3H]-liraglutide dose to healthy subjects, the major component in plasma was intact liraglutide. Liraglutide is endogenously metabolized in a similar manner to large proteins without a specific organ as a major route of elimination.

Excretion

Following a [3H]-liraglutide dose, intact liraglutide was not detected in urine or feces. Only a minor part of the administered radioactivity was excreted as liraglutide-related metabolites in urine or feces (6% and 5%, respectively). The majority of urine and feces radioactivity was excreted during the first 6-8 days.

Specific Populations

Geriatric Patients

Age had no effect on the pharmacokinetics of VICTOZA based on a pharmacokinetic study in healthy elderly subjects (65 to 83 years) and population pharmacokinetic analyses of patients 18 to 80 years of age [see Use in Specific Populations (8.5)].

Pediatric Patients

A population pharmacokinetic analysis was conducted for VICTOZA using data from 72 pediatric patients (10 to 17 years of age) with type 2 diabetes mellitus. The pharmacokinetic profile of VICTOZA in the pediatric patients was consistent with that in adults.

Male and Female Patients

Based on the results of population pharmacokinetic analyses, females have 25% lower weight-adjusted clearance of VICTOZA compared to males.

Race or Ethnic Groups

Race and ethnicity had no effect on the pharmacokinetics of VICTOZA based on the results of population pharmacokinetic analyses that included White, Black or African American, Asian and Hispanic or Latino/Non-Hispanic or Latino subjects.

Body Weight

Body weight significantly affects the pharmacokinetics of VICTOZA based on results of population pharmacokinetic analyses. The exposure of liraglutide decreases with an increase in baseline body weight. However, the 1.2 mg and 1.8 mg daily doses of VICTOZA provided adequate systemic exposures over the body weight range of 40 – 160 kg evaluated in the clinical trials. Liraglutide was not studied in patients with body weight >160 kg.

Patients with Renal Impairment

The single-dose pharmacokinetics of VICTOZA were evaluated in patients with varying degrees of renal impairment. Patients with mild (estimated creatinine clearance 50-80 mL/min) to severe (estimated creatinine clearance <30 mL/min) renal impairment and subjects with end-stage renal disease requiring dialysis were included in the trial. Compared to healthy subjects, liraglutide AUC in mild, moderate, and severe renal impairment and in end-stage renal disease was on average 35%, 19%, 29% and 30% lower, respectively [see Use in Specific Populations (8.6)].

Patients with Hepatic Impairment

The single-dose pharmacokinetics of VICTOZA were evaluated in patients with varying degrees of hepatic impairment. Patients with mild (Child Pugh score 5-6) to severe (Child Pugh score > 9) hepatic impairment were included in the trial. Compared to healthy subjects, liraglutide AUC in patients with mild, moderate and severe hepatic impairment was on average 11%, 14% and 42% lower, respectively [see Use in Specific Populations (8.7)].

Drug Interaction Studies

In vitro assessment of drug-drug interactions

VICTOZA has low potential for pharmacokinetic drug-drug interactions related to cytochrome P450 (CYP) and plasma protein binding.

In vivo assessment of drug-drug interactions

The drug-drug interaction studies were performed at steady state with VICTOZA 1.8 mg/day. Before administration of concomitant treatment, subjects underwent a 0.6 mg weekly dose increase to reach the maximum dose of 1.8 mg/day. Administration of the interacting drugs was timed so that Cmax of VICTOZA (8-12 h) would coincide with the absorption peak of the co-administered drugs.

Digoxin

A single dose of digoxin 1 mg was administered 7 hours after the dose of VICTOZA at steady state. The concomitant administration with VICTOZA resulted in a reduction of digoxin AUC by 16%; Cmax decreased by 31%. Digoxin median time to maximal concentration (Tmax) was delayed from 1 h to 1.5 h.

Lisinopril

A single dose of lisinopril 20 mg was administered 5 minutes after the dose of VICTOZA at steady state. The co-administration with VICTOZA resulted in a reduction of lisinopril AUC by 15%; Cmax decreased by 27%. Lisinopril median Tmax was delayed from 6 h to 8 h with VICTOZA.

Atorvastatin

VICTOZA did not change the overall exposure (AUC) of atorvastatin following a single dose of atorvastatin 40 mg, administered 5 hours after the dose of VICTOZA at steady state. Atorvastatin Cmax was decreased by 38% and median Tmax was delayed from 1 h to 3 h with VICTOZA.

Acetaminophen

VICTOZA did not change the overall exposure (AUC) of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after the dose of VICTOZA at steady state. Acetaminophen Cmax was decreased by 31% and median Tmax was delayed up to 15 minutes.

Griseofulvin

VICTOZA did not change the overall exposure (AUC) of griseofulvin following co-administration of a single dose of griseofulvin 500 mg with VICTOZA at steady state. Griseofulvin Cmax increased by 37% while median Tmax did not change.

Oral Contraceptives

A single dose of an oral contraceptive combination product containing 0.03 mg ethinylestradiol and 0.15 mg levonorgestrel was administered under fed conditions and 7 hours after the dose of VICTOZA at steady state. VICTOZA lowered ethinylestradiol and levonorgestrel Cmax by 12% and 13%, respectively. There was no effect of VICTOZA on the overall exposure (AUC) of ethinylestradiol. VICTOZA increased the levonorgestrel AUC0-∞ by 18%. VICTOZA delayed Tmax for both ethinylestradiol and levonorgestrel by 1.5 h.

Insulin Detemir

No pharmacokinetic interaction was observed between VICTOZA and insulin detemir when separate subcutaneous injections of insulin detemir 0.5 Unit/kg (single-dose) and VICTOZA 1.8 mg (steady state) were administered in patients with type 2 diabetes mellitus.

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those with VICTOZA or other liraglutide products.

A subset of VICTOZA-treated patients (1104 of 2501, 44%) in five adult double-blind clinical trials of 26 weeks duration or longer were tested for the presence of anti-liraglutide antibodies at the end of treatment [see Clinical Studies (14.1)] and 102/1104 (9%) of VICTOZA-treated patients developed anti-liraglutide antibodies. Of these 102 VICTOZA-treated patients, 56 (5%) patients developed antibodies that cross-reacted with native GLP-1. These cross-reacting antibodies were not tested for neutralizing effect against native GLP-1, and thus the potential for clinically significant neutralization of native GLP-1 was not assessed. Antibodies that had a neutralizing effect on liraglutide in an in vitro assay occurred in 12 (1%) of the VICTOZA-treated patients. There was no identified clinically significant effect of anti-liraglutide antibodies on effectiveness of VICTOZA.

In five double-blind adult glycemic control trials of VICTOZA, events from a composite of adverse events potentially related to immunogenicity (e.g., urticaria, angioedema) occurred among 0.8% of VICTOZA-treated patients and among 0.4% of comparator-treated patients. Urticaria accounted for approximately one-half of the events in this composite for VICTOZA-treated patients. Patients who developed anti-liraglutide antibodies were not more likely to develop events from the immunogenicity events composite than were patients who did not develop anti-liraglutide antibodies.

In the LEADER trial [see Clinical Studies (14.3)], anti-liraglutide antibodies were detected in 11 out of the 1247 (0.9%) adult VICTOZA-treated patients with antibody measurements. Of the 11 adult VICTOZA-treated patients who developed anti-liraglutide antibodies, none were observed to develop neutralizing antibodies to liraglutide, and 5 patients (0.4%) developed cross-reacting antibodies against native GLP-1.

In a clinical trial with pediatric patients aged 10 years and older [see Clinical Studies (14.2)], anti-liraglutide antibodies were detected in 1 (2%) VICTOZA treated patient at week 26 and 5 (9%) VICTOZA treated patients at week 53. None of the 5 patients had antibodies cross reactive to native GLP-1 or had neutralizing antibodies.

A 104-week carcinogenicity study was conducted in male and female CD-1 mice at doses of 0.03, 0.2, 1.0, and 3.0 mg/kg/day liraglutide administered by bolus subcutaneous injection yielding systemic exposures 0.2-, 2-, 10- and 45-times the human exposure, respectively, at the MRHD of 1.8 mg/day based on plasma AUC comparison. A dose-related increase in benign thyroid C-cell adenomas was seen in the 1.0 and the 3.0 mg/kg/day groups with incidences of 13% and 19% in males and 6% and 20% in females, respectively. C-cell adenomas did not occur in control groups or 0.03 and 0.2 mg/kg/day groups. Treatment-related malignant C-cell carcinomas occurred in 3% of females in the 3.0 mg/kg/day group. Thyroid C-cell tumors are rare findings during carcinogenicity testing in mice. A treatment-related increase in fibrosarcomas was seen on the dorsal skin and subcutis, the body surface used for drug injection, in males in the 3 mg/kg/day group. These fibrosarcomas were attributed to the high local concentration of drug near the injection site. The liraglutide concentration in the clinical formulation (6 mg/mL) is 10-times higher than the concentration in the formulation used to administer 3 mg/kg/day liraglutide to mice in the carcinogenicity study (0.6 mg/mL).

A 104-week carcinogenicity study was conducted in male and female Sprague Dawley rats at doses of 0.075, 0.25 and 0.75 mg/kg/day liraglutide administered by bolus subcutaneous injection with exposures 0.5-, 2- and 8-times the human exposure, respectively, resulting from the MRHD based on plasma AUC comparison. A treatment-related increase in benign thyroid C-cell adenomas was seen in males in 0.25 and 0.75 mg/kg/day liraglutide groups with incidences of 12%, 16%, 42%, and 46% and in all female liraglutide-treated groups with incidences of 10%, 27%, 33%, and 56% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups, respectively. A treatment-related increase in malignant thyroid C-cell carcinomas was observed in all male liraglutide-treated groups with incidences of 2%, 8%, 6%, and 14% and in females at 0.25 and 0.75 mg/kg/day with incidences of 0%, 0%, 4%, and 6% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups, respectively. Thyroid C-cell carcinomas are rare findings during carcinogenicity testing in rats.

Studies in mice demonstrated that liraglutide-induced C-cell proliferation was dependent on the GLP-1 receptor and that liraglutide did not cause activation of the REarranged during Transfection (RET) proto-oncogene in thyroid C-cells.

Human relevance of thyroid C-cell tumors in mice and rats is unknown and has not been determined by clinical studies or nonclinical studies [see Boxed Warning and Warnings and Precautions (5.1)].

Liraglutide was negative with and without metabolic activation in the Ames test for mutagenicity and in a human peripheral blood lymphocyte chromosome aberration test for clastogenicity. Liraglutide was negative in repeat-dose in vivo micronucleus tests in rats.

In rat fertility studies using subcutaneous doses of 0.1, 0.25 and 1.0 mg/kg/day liraglutide, males were treated for 4 weeks prior to and throughout mating and females were treated 2 weeks prior to and throughout mating until gestation day 17. No direct adverse effects on male fertility was observed at doses up to 1.0 mg/kg/day, a high dose yielding an estimated systemic exposure 11- times the human exposure at the MRHD, based on plasma AUC. In female rats, an increase in early embryonic deaths occurred at 1.0 mg/kg/day. Reduced body weight gain and food consumption were observed in females at the 1.0 mg/kg/day dose.

In glycemic control trials in adults, VICTOZA has been studied as monotherapy and in combination with one or two oral anti-diabetic medications or basal insulin. VICTOZA was also studied in a cardiovascular outcomes trial (LEADER trial).

In each of the placebo controlled trials, treatment with VICTOZA produced clinically and statistically significant improvements in hemoglobin A1c and fasting plasma glucose (FPG) compared to placebo.

All VICTOZA-treated patients started at 0.6 mg/day. The dose was increased in weekly intervals by 0.6 mg to reach 1.2 mg or 1.8 mg for patients randomized to these higher doses. VICTOZA 0.6 mg is not effective for glycemic control and is intended only as a starting dose to reduce gastrointestinal intolerance [see Dosage and Administration (2)].

Monotherapy

In this 52-week trial, 746 adult patients with type 2 diabetes mellitus were randomized to VICTOZA 1.2 mg, VICTOZA 1.8 mg, or glimepiride 8 mg. Patients who were randomized to glimepiride were initially treated with 2 mg daily for two weeks, increasing to 4 mg daily for another two weeks, and finally increasing to 8 mg daily. Treatment with VICTOZA 1.8 mg and 1.2 mg resulted in a statistically significant reduction in HbA1c compared to glimepiride (Table 3). The percentage of patients who discontinued due to ineffective therapy was 3.6% in the VICTOZA 1.8 mg treatment group, 6.0% in the VICTOZA 1.2 mg treatment group, and 10.1% in the glimepiride-treatment group.

The mean age of participants was 53 years, and the mean duration of diabetes was 5 years. Participants were 49.7% male, 77.5% White, 12.6% Black or African American and 35.0% of Hispanic or Latino ethnicity. The mean BMI was 33.1 kg/m2.

Table 3. Results of a 52-week Monotherapy Trial in Adults with Type 2 Diabetes Mellitusa

<div class="scrollingtable"><table width="87.44%"> <col width="44%"/> <col width="17%"/> <col width="18%"/> <col width="22%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">VICTOZA </span> </p> <p> <span class="Bold">1.8 mg</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">VICTOZA </span> </p> <p> <span class="Bold">1.2 mg</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">Glimepiride 8 mg</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Intent-to-Treat Population (N)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">246</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">251</p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>248</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">HbA<span class="Sub">1c</span> (%) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="top"> <p class="First"> Baseline</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">8.2</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">8.2</p> </td><td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>8.2</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-1.1</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-0.8</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>-0.5</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Difference from glimepiride arm (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-0.6**</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-0.3*</p> </td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> 95% Confidence Interval</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-0.8, -0.4)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-0.5, -0.1)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Percentage of patients achieving HbA<span class="Sub">1c</span> &lt;7%</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">51</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">43</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>28</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Fasting Plasma Glucose (mg/dL) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="top"> <p class="First"> Baseline</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">172</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">168</p> </td><td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>172</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-26</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-15 </p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>-5 </dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Difference from glimepiride arm (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-20**</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-10*</p> </td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> 95% Confidence Interval</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-29, -12)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-19, -1)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Body Weight (kg) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Baseline</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">92.6</p> </td><td align="center" class="Lrule" valign="top"> <p class="First">92.1</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>93.3</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-2.5</p> </td><td align="center" class="Lrule" valign="top"> <p class="First">-2.1</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>+1.1</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Difference from glimepiride arm (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-3.6**</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-3.2**</p> </td><td class="Lrule Rrule" valign="top"></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> 95% Confidence Interval</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-4.3, -2.9)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-3.9, -2.5)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> </tbody> </table></div>

aIntent-to-treat population using last observation on study

bLeast squares mean adjusted for baseline value

*p-value <0.05

**p-value <0.0001

Figure 3. Mean HbA1c for Adult Patients with Type 2 Diabetes Mellitus who Completed the 52-week Trial and for the Last Observation Carried Forward (LOCF, intent-to-treat) data at Week 52 (Monotherapy)

Combination Therapy

Add-on to Metformin

In this 26-week trial, 1,091 adult patients with type 2 diabetes mellitus were randomized to VICTOZA 0.6 mg, VICTOZA 1.2 mg, VICTOZA 1.8 mg, placebo, or glimepiride 4 mg (one-half of the maximal approved dose in the United States), all as add-on to metformin. Randomization occurred after a 6-week run-in period consisting of a 3-week initial forced metformin titration period followed by a maintenance period of another 3 weeks. During the titration period, doses of metformin were increased up to 2000 mg/day. Treatment with VICTOZA 1.2 mg and 1.8 mg as add-on to metformin resulted in a significant mean HbA1c reduction relative to placebo add-on to metformin and resulted in a similar mean HbA1c reduction relative to glimepiride 4 mg add-on to metformin (Table 4). The percentage of patients who discontinued due to ineffective therapy was 5.4% in the VICTOZA 1.8 mg + metformin treatment group, 3.3% in the VICTOZA 1.2 mg + metformin treatment group, 23.8% in the placebo + metformin treatment group, and 3.7% in the glimepiride + metformin treated group.

The mean age of participants was 57 years, and the mean duration of diabetes was 7 years. Participants were 58.2% male, 87.1% White and 2.4% Black or African American. The mean BMI was 31.0 kg/m2.

Table 4. Results of a 26-week Trial of VICTOZA as Add-on to Metformin in Adults with Type 2 Diabetes Mellitusa

<div class="scrollingtable"><table width="100%"> <col width="42%"/> <col width="11%"/> <col width="11%"/> <col width="18%"/> <col width="18%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">VICTOZA </span> </p> <p> <span class="Bold">1.8 mg</span> +</p> <p> <span class="Bold">Metformin</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">VICTOZA </span> </p> <p> <span class="Bold">1.2 mg </span>+</p> <p> <span class="Bold">Metformin</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">Placebo + </span> </dd> <dt> </dt> <dd> <span class="Bold">Metformin</span> </dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Glimepiride </span> </p> <p> <span class="Bold">4 mg</span><span class="Sup">† </span>+</p> <dl> <dt> </dt> <dd> <span class="Bold">Metformin</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Intent-to-Treat Population (N)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">242</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">240</p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>121</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>242</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">HbA<span class="Sub">1c</span> (%) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="top"> <p class="First"> Baseline</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">8.4</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">8.3</p> </td><td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>8.4</dd> </dl> </td><td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>8.4</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-1.0</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-1.0</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>+0.1</dd> </dl> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>-1.0</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Difference from placebo + metformin arm (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-1.1**</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-1.1**</p> </td><td class="Lrule Rrule" valign="top"></td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> 95% Confidence Interval</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">(-1.3, -0.9)</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">(-1.3, -0.9)</p> </td><td class="Lrule Rrule" valign="top"></td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Difference from glimepiride + metformin arm (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.0</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.0</p> </td><td class="Lrule Rrule" valign="top"></td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> 95% Confidence Interval</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-0.2, 0.2)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-0.2, 0.2)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Percentage of patients achieving HbA<span class="Sub">1c</span> &lt;7%</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">42</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">35</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>11</dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>36</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Fasting Plasma Glucose (mg/dL) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="top"> <p class="First"> Baseline</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">181</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">179 </p> </td><td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>182</dd> </dl> </td><td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>180</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-30 </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-30</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>+7 </dd> </dl> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>-24</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Difference from placebo + metformin arm (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-38**</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-37**</p> </td><td class="Lrule Rrule" valign="top"></td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> 95% Confidence Interval</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">(-48, -27)</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">(-47, -26)</p> </td><td class="Lrule Rrule" valign="top"></td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Difference from glimepiride + metformin arm (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-7</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-6</p> </td><td class="Lrule Rrule" valign="top"></td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> 95% Confidence Interval</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-16, 2)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-15, 3)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Body Weight (kg) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="top"> <p class="First"> Baseline</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">88.0</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">88.5</p> </td><td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>91.0</dd> </dl> </td><td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>89.0</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-2.8</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-2.6</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>-1.5</dd> </dl> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>+1.0</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Difference from placebo + metformin arm (adjusted mean)<span class="Sup"> b</span> </p> <p> 95% Confidence Interval</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-1.3*</p> <p>(-2.2, -0.4)</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-1.1*</p> <p>(-2.0, -0.2)</p> </td><td class="Lrule Rrule" valign="top"></td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Difference from glimepiride + metformin arm (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-3.8**</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-3.5**</p> </td><td class="Lrule Rrule" valign="top"></td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> 95% Confidence Interval</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-4.5, -3.0)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-4.3, -2.8)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr class="Last"> <td class="Botrule Toprule" colspan="5" valign="top"> <p class="First"> <span class="Sup">a</span>Intent-to-treat population using last observation on study </p> <p> <span class="Sup">b</span>Least squares mean adjusted for baseline value</p> <p> <span class="Sup">†</span> For glimepiride, one-half of the maximal approved United States dose.</p> <p>*p-value &lt;0.05 </p> <p>**p-value &lt;0.0001</p> </td> </tr> </tbody> </table></div>

VICTOZA Compared to Sitagliptin, Both as Add-on to Metformin

In this 26–week, open-label trial, 665 adult patients with type 2 diabetes mellitus on a background of metformin ≥1,500 mg per day were randomized to VICTOZA 1.2 mg once daily, VICTOZA 1.8 mg once daily or sitagliptin 100 mg once daily, all dosed according to approved labeling. Patients were to continue their current treatment on metformin at a stable, pre-trial dose level and dosing frequency.

The mean age of participants was 56 years, and the mean duration of diabetes was 6 years. Participants were 52.9% male, 86.6% White, 7.2% Black or African American and 16.2% of Hispanic or Latino ethnicity. The mean BMI was 32.8 kg/m2.

The primary endpoint was the change in HbA1c from baseline to Week 26. Treatment with VICTOZA 1.2 mg and VICTOZA 1.8 mg resulted in statistically significant reductions in HbA1c relative to sitagliptin 100 mg (Table 5). The percentage of patients who discontinued due to ineffective therapy was 3.1% in the VICTOZA 1.2 mg group, 0.5% in the VICTOZA 1.8 mg treatment group, and 4.1% in the sitagliptin 100 mg treatment group. From a mean baseline body weight of 94 kg, there was a mean reduction of 2.7 kg for VICTOZA 1.2 mg, 3.3 kg for VICTOZA 1.8 mg, and 0.8 kg for sitagliptin 100 mg.

Table 5. Results of a 26-week Open-label Trial of VICTOZA Compared to Sitagliptin (both in combination with metformin) in Adults with Type 2 Diabetes Mellitusa

<div class="scrollingtable"><table width="99.54%"> <col width="59%"/> <col width="13%"/> <col width="14%"/> <col width="15%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">VICTOZA </span> </p> <p> <span class="Bold">1.8 mg</span> +</p> <p> <span class="Bold">Metformin</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">VICTOZA </span> </p> <p> <span class="Bold">1.2 mg</span> +</p> <p> <span class="Bold">Metformin</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Sitagliptin </span> </p> <p> <span class="Bold">100 mg +</span> </p> <p> <span class="Bold">Metformin</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Intent-to-Treat Population (N)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">218</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">221</p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>219</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">HbA<span class="Sub">1c</span> (%) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Baseline</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">8.4</p> </td><td align="center" class="Lrule" valign="top"> <p class="First">8.4</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>8.5</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-1.5</p> </td><td align="center" class="Lrule" valign="top"> <p class="First">-1.2</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>-0.9</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Difference from sitagliptin arm (adjusted mean)<span class="Sup"> b</span> </p> <p> 95% Confidence Interval</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-0.6**</p> <p>(-0.8, -0.4)</p> </td><td align="center" class="Lrule" valign="top"> <p class="First">-0.3**</p> <p>(-0.5, -0.2)</p> </td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Percentage of patients achieving HbA<span class="Sub">1c</span> &lt;7%</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">56</p> </td><td align="center" class="Lrule" valign="top"> <p class="First">44</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>22</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Fasting Plasma Glucose (mg/dL) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="top"> <p class="First"> Baseline</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">179</p> </td><td align="center" class="Lrule Toprule" valign="top"> <p class="First">182</p> </td><td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>180</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-39</p> </td><td align="center" class="Lrule" valign="top"> <p class="First">-34</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>-15</dd> </dl> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> Difference from sitagliptin arm (adjusted mean)<span class="Sup"> b</span> </p> <p> 95% Confidence Interval</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-24**</p> <p>(-31, -16)</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">-19**</p> <p>(-26, -12)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> </tbody> </table></div>

aIntent-to-treat population using last observation on study

bLeast squares mean adjusted for baseline value

**p-value <0.0001

Figure 4. Mean HbA1c for Adult Patients with Type 2 Diabetes Mellitus who Completed the 26-week Trial and for the Last Observation Carried Forward (LOCF, intent-to-treat) data at Week 26

Combination Therapy with Metformin and Insulin

This 26-week open-label trial enrolled 988 adult patients with type 2 diabetes mellitus with inadequate glycemic control (HbA1c 7-10%) on metformin (≥1,500 mg/day) alone or inadequate glycemic control (HbA1c 7-8.5%) on metformin (≥1500 mg/day) and a sulfonylurea. Patients who were on metformin and a sulfonylurea discontinued the sulfonylurea then all patients entered a 12-week run-in period during which they received add-on therapy with VICTOZA titrated to 1.8 mg once-daily. At the end of the run-in period, 498 patients (50%) achieved HbA1c <7% with VICTOZA 1.8 mg and metformin and continued treatment in a non-randomized, observational arm. Another 167 patients (17%) withdrew from the trial during the run-in period with approximately one-half of these patients doing so because of gastrointestinal adverse reactions [see Adverse Reactions (6.1)]. The remaining 323 patients with HbA1c ≥7% (33% of those who entered the run-in period) were randomized to 26 weeks of once-daily insulin detemir administered in the evening as add-on therapy (N=162) or to continued, unchanged treatment with VICTOZA 1.8 mg and metformin (N=161). The starting dose of insulin detemir was 10 units/day and the mean dose at the end of the 26-week randomized period was 39 units/day. During the 26 week randomized treatment period, the percentage of patients who discontinued due to ineffective therapy was 11.2% in the group randomized to continued treatment with VICTOZA 1.8 mg and metformin and 1.2% in the group randomized to add-on therapy with insulin detemir.

The mean age of participants was 57 years, and the mean duration of diabetes was 8 years. Participants were 55.7% male, 91.3% White, 5.6% Black or African American and 12.5% of Hispanic or Latino ethnicity. The mean BMI was 34.0 kg/m2.

Treatment with insulin detemir as add-on to VICTOZA 1.8 mg + metformin resulted in statistically significant reductions in HbA1c and FPG compared to continued, unchanged treatment with VICTOZA 1.8 mg + metformin alone (Table 6). From a mean baseline body weight of 96 kg after randomization, there was a mean reduction of 0.3 kg in the patients who received insulin detemir add-on therapy compared to a mean reduction of 1.1 kg in the patients who continued on unchanged treatment with VICTOZA 1.8 mg + metformin alone.

Table 6. Results of a 26-week Open-label Trial of Insulin detemir as add on to VICTOZA + Metformin Compared to Continued Treatment with VICTOZA + Metformin alone in Adult Patients with Type 2 Diabetes Mellitus not Achieving HbA1c < 7% after 12 weeks of Metformin and VICTOZAa

<div class="scrollingtable"><table width="95.04%"> <col width="46%"/> <col width="26%"/> <col width="27%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Insulin detemir + VICTOZA + Metformin</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">VICTOZA + Metformin</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Intent-to-Treat Population (N)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">162</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">157</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">HbA<span class="Sub">1c</span> (%) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="top"> <p class="First"> Baseline (week 0)</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">7.6</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">7.6</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-0.5</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> Difference from VICTOZA + metformin arm (LS mean)<span class="Sup"> b</span> </dd> </dl> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-0.5**</p> </td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> 95% Confidence Interval</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-0.7, -0.4)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Percentage of patients achieving HbA<span class="Sub">1c</span> &lt;7% </p> </td><td align="center" class="Botrule Toprule" valign="top"> <p class="First">43</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">17</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Fasting Plasma Glucose (mg/dL) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Baseline (week 0)</p> </td><td align="center" valign="top"> <p class="First">166 </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">159</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)</p> </td><td align="center" valign="top"> <p class="First">-39 </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-7</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> Difference from VICTOZA + metformin arm (LS mean)<span class="Sup"> b</span> </dd> </dl> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-31** </p> </td><td class="Lrule Rrule" valign="top"></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> 95% Confidence Interval</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-39, -23)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> </tbody> </table></div>

aIntent-to-treat population using last observation on study

bLeast squares mean adjusted for baseline value

**p-value <0.0001

Add-on to Sulfonylurea

In this 26-week trial, 1,041 adult patients with type 2 diabetes mellitus were randomized to VICTOZA 0.6 mg, VICTOZA 1.2 mg, VICTOZA 1.8 mg, placebo, or rosiglitazone 4 mg (one-half of the maximal approved dose in the United States), all as add-on to glimepiride. Randomization occurred after a 4-week run-in period consisting of an initial, 2-week, forced-glimepiride titration period followed by a maintenance period of another 2 weeks. During the titration period, doses of glimepiride were increased to 4 mg/day. The doses of glimepiride could be reduced (at the discretion of the investigator) from 4 mg/day to 3 mg/day or 2 mg/day (minimum) after randomization, in the event of unacceptable hypoglycemia or other adverse events.

The mean age of participants was 56 years, and the mean duration of diabetes was 8 years. Participants were 49.4% male, 64.4% White and 2.8% Black or African American. The mean BMI was 29.9 kg/m2.

Treatment with VICTOZA 1.2 mg and 1.8 mg as add-on to glimepiride resulted in a statistically significant reduction in mean HbA1c compared to placebo add-on to glimepiride (Table 7). The percentage of patients who discontinued due to ineffective therapy was 3.0% in the VICTOZA 1.8 mg + glimepiride treatment group, 3.5% in the VICTOZA 1.2 mg + glimepiride treatment group, 17.5% in the placebo + glimepiride treatment group, and 6.9% in the rosiglitazone + glimepiride treatment group.

Table 7. Results of a 26-week Trial of VICTOZA as add-on to Sulfonylurea in Adult Patients with Type 2 Diabetes Mellitusa

<div class="scrollingtable"><table width="97.8%"> <col width="35%"/> <col width="13%"/> <col width="13%"/> <col width="19%"/> <col width="20%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">VICTOZA </span> </p> <p> <span class="Bold">1.8 mg</span> +</p> <p> <span class="Bold">Glimepiride</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">VICTOZA </span> </p> <p> <span class="Bold">1.2 mg </span>+</p> <p> <span class="Bold">Glimepiride</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="middle"> <dl> <dt> </dt> <dd> <span class="Bold">Placebo +</span> </dd> <dt> </dt> <dd> <span class="Bold">Glimepiride</span> </dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="middle"> <dl> <dt> </dt> <dd> <span class="Bold">Rosiglitazone</span> </dd> <dt> </dt> <dd> <span class="Bold"> 4 mg</span><span class="Sup">†</span><span class="Bold"> +</span> </dd> <dt> </dt> <dd> <span class="Bold">Glimepiride</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Intent-to-Treat Population (N)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">234</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">228</p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>114</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>231</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">HbA<span class="Sub">1c</span> (%) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd> Baseline</dd> </dl> </td><td align="center" class="Rrule Toprule" valign="top"> <p class="First">8.5</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">8.5</p> </td><td class="Lrule Toprule" valign="top"> <dl> <dt> </dt> <dd>8.4</dd> </dl> </td><td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>8.4</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> Change from baseline (adjusted mean)<span class="Sup"> b</span> </dd> </dl> </td><td align="center" class="Rrule" valign="top"> <p class="First">-1.1</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-1.1</p> </td><td class="Lrule" valign="top"> <dl> <dt> </dt> <dd>+0.2</dd> </dl> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>-0.4</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> Difference from placebo + glimepiride arm (adjusted mean)<span class="Sup"> b</span> </dd> </dl> </td><td align="center" class="Rrule" valign="top"> <p class="First">-1.4**</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-1.3**</p> </td><td class="Lrule" valign="top"></td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> 95% Confidence Interval</dd> </dl> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">(-1.6, -1.1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-1.5, -1.1)</p> </td><td class="Botrule Lrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Percentage of patients achieving HbA<span class="Sub">1c</span> &lt;7%</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">42</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">35</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>7</dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>22</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Fasting Plasma Glucose (mg/dL) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd> Baseline</dd> </dl> </td><td align="center" class="Rrule Toprule" valign="top"> <p class="First">174</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">177</p> </td><td class="Lrule Toprule" valign="top"> <dl> <dt> </dt> <dd>171</dd> </dl> </td><td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>179</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> Change from baseline (adjusted mean)<span class="Sup"> b</span> </dd> </dl> </td><td align="center" class="Rrule" valign="top"> <p class="First">-29</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-28 </p> </td><td class="Lrule" valign="top"> <dl> <dt> </dt> <dd>+18 </dd> </dl> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>-16</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> Difference from placebo + glimepiride arm (adjusted mean)<span class="Sup"> b</span> </dd> </dl> </td><td align="center" class="Rrule" valign="top"> <p class="First">-47**</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-46**</p> </td><td class="Lrule" valign="top"></td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> 95% Confidence Interval</dd> </dl> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">(-58, -35)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-58, -35)</p> </td><td class="Botrule Lrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">Body Weight (kg) (Mean)</span> </dd> </dl> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> Baseline</dd> </dl> </td><td align="center" class="Rrule" valign="top"> <p class="First">83.0</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">80.0</p> </td><td class="Lrule" valign="top"> <dl> <dt> </dt> <dd>81.9</dd> </dl> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>80.6</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> Change from baseline (adjusted mean)<span class="Sup"> b</span> </dd> </dl> </td><td align="center" class="Rrule" valign="top"> <p class="First">-0.2</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">+0.3</p> </td><td class="Lrule" valign="top"> <dl> <dt> </dt> <dd>-0.1</dd> </dl> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>+2.1</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> Difference from placebo + glimepiride arm (adjusted mean)<span class="Sup"> b</span> </dd> </dl> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-0.1</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">0.4</p> </td><td class="Lrule Rrule" valign="top"></td><td class="Lrule Rrule" valign="top"></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> 95% Confidence Interval</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-0.9, 0.6)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-0.4, 1.2)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> </tbody> </table></div>

aIntent-to-treat population using last observation on study

bLeast squares mean adjusted for baseline value

† For rosiglitazone, one-half of the maximal approved United States dose.

**p-value <0.0001

Add-on to Metformin and Sulfonylurea

In this 26-week trial, 581 adult patients with type 2 diabetes mellitus were randomized to VICTOZA 1.8 mg, placebo, or insulin glargine, all as add-on to metformin and glimepiride. Randomization took place after a 6-week run-in period consisting of a 3-week forced metformin and glimepiride titration period followed by a maintenance period of another 3 weeks. During the titration period, doses of metformin and glimepiride were to be increased up to 2,000 mg/day and 4 mg/day, respectively. After randomization, patients randomized to VICTOZA 1.8 mg underwent a 2 week period of titration with VICTOZA. During the trial, the VICTOZA and metformin doses were fixed, although glimepiride and insulin glargine doses could be adjusted. Patients titrated glargine twice-weekly during the first 8 weeks of treatment based on self-measured fasting plasma glucose on the day of titration. After Week 8, the frequency of insulin glargine titration was left to the discretion of the investigator, but, at a minimum, the glargine dose was to be revised, if necessary, at Weeks 12 and 18. Only 20% of glargine-treated patients achieved the pre-specified target fasting plasma glucose of ≤100 mg/dL. Therefore, optimal titration of the insulin glargine dose was not achieved in most patients.

The mean age of participants was 58 years, and the mean duration of diabetes was 9 years. Participants were 56.5% male, 75.0% White and 3.6% Black or African American. The mean BMI was 30.5 kg/m2.

Treatment with VICTOZA as add-on to glimepiride and metformin resulted in a statistically significant mean reduction in HbA1c compared to placebo add-on to glimepiride and metformin (Table 8). The percentage of patients who discontinued due to ineffective therapy was 0.9% in the VICTOZA 1.8 mg + metformin + glimepiride treatment group, 0.4% in the insulin glargine + metformin + glimepiride treatment group, and 11.3% in the placebo + metformin + glimepiride treatment group.

Table 8. Results of a 26-week Trial of VICTOZA as Add-on to Metformin and Sulfonylurea in Adult Patients with Type 2 Diabetes Mellitusa

<div class="scrollingtable"><table width="99.54%"> <col width="59%"/> <col width="14%"/> <col width="14%"/> <col width="14%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">VICTOZA </span> </p> <p> <span class="Bold">1.8 mg</span> +</p> <p> <span class="Bold">Metformin +</span> </p> <p> <span class="Bold">Glimepiride</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Placebo +</span> </p> <p> <span class="Bold">Metformin +</span> </p> <p> <span class="Bold">Glimepiride</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Insulin glargine<span class="Sup">† </span>+</span> </p> <p> <span class="Bold">Metformin +</span> </p> <p> <span class="Bold">Glimepiride</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Intent-to-Treat Population (N)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">230</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">114</p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>232</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">HbA<span class="Sub">1c</span> (%) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Baseline</p> </td><td align="center" class="Rrule" valign="top"> <p class="First">8.3</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">8.3</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>8.1</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Rrule" valign="top"> <p class="First">-1.3</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-0.2</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>-1.1</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> Difference from placebo + metformin + glimepiride arm (adjusted mean)<span class="Sup"> b</span> </dd> </dl> </td><td align="center" class="Rrule" valign="top"> <p class="First">-1.1**</p> </td><td class="Lrule Rrule" valign="top"></td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> 95% Confidence Interval</dd> </dl> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">(-1.3, -0.9)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Percentage of patients achieving HbA<span class="Sub">1c</span> &lt;7%</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">53</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">15</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>46</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Fasting Plasma Glucose (mg/dL) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="top"> <p class="First"> Baseline</p> </td><td align="center" class="Rrule Toprule" valign="top"> <p class="First">165</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">170</p> </td><td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>164</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Rrule" valign="top"> <p class="First">-28</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">+10</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>-32 </dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> Difference from placebo + metformin + glimepiride arm (adjusted mean)<span class="Sup"> b</span> </dd> </dl> </td><td align="center" class="Rrule" valign="top"> <p class="First">-38**</p> </td><td class="Lrule Rrule" valign="top"></td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> 95% Confidence Interval</dd> </dl> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">(-46, -30)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Body Weight (kg) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Baseline</p> </td><td align="center" class="Rrule" valign="top"> <p class="First">85.8</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">85.4</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>85.2</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Rrule" valign="top"> <p class="First">-1.8</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-0.4</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>1.6</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> Difference from placebo + metformin + glimepiride arm (adjusted mean)<span class="Sup"> b</span> </dd> </dl> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-1.4*</p> </td><td class="Lrule Rrule" valign="top"></td><td class="Lrule Rrule" valign="top"></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> 95% Confidence Interval</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-2.1, -0.7)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> </tbody> </table></div>

aIntent-to-treat population using last observation on study

bLeast squares mean adjusted for baseline value

† For insulin glargine, optimal titration regimen was not achieved for 80% of patients.

*p-value <0.05

**p-value <0.0001

VICTOZA Compared to Exenatide, Both as Add-on to Metformin and/or Sulfonylurea Therapy

In this 26–week, open-label trial, 464 adult patients with type 2 diabetes mellitus on a background of metformin monotherapy, sulfonylurea monotherapy or a combination of metformin and sulfonylurea were randomized to once daily VICTOZA 1.8 mg or exenatide 10 mcg twice daily. Maximally tolerated doses of background therapy were to remain unchanged for the duration of the trial. Patients randomized to exenatide started on a dose of 5 mcg twice-daily for 4 weeks and then were escalated to 10 mcg twice daily.

The mean age of participants was 57 years, and the mean duration of diabetes was 8 years. Participants were 51.9% male, 91.8% White, 5.4% Black or African American and 12.3% of Hispanic or Latino ethnicity. The mean BMI was 32.9 kg/m2.

Treatment with VICTOZA 1.8 mg resulted in statistically significant reductions in HbA1c and FPG relative to exenatide (Table 9). The percentage of patients who discontinued for ineffective therapy was 0.4% in the VICTOZA treatment group and 0% in the exenatide treatment group. Both treatment groups had a mean decrease from baseline in body weight of approximately 3 kg.

Table 9. Results of a 26-week Open-label trial of VICTOZA versus Exenatide (both in combination with metformin and/or sulfonylurea) in Adult Patients with Type 2 Diabetes Mellitusa

<div class="scrollingtable"><table width="90.66%"> <col width="58%"/> <col width="20%"/> <col width="22%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">VICTOZA </span> </p> <p> <span class="Bold">1.8 mg once daily</span> </p> <p> <span class="Bold">+ metformin and/or sulfonylurea</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Exenatide</span> </p> <p> <span class="Bold">10 mcg twice daily </span> </p> <p> <span class="Bold">+ metformin and/or sulfonylurea </span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Intent-to-Treat Population (N)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">233</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">231</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">HbA<span class="Sub">1c</span> (%) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="top"> <p class="First"> Baseline</p> </td><td align="center" class="Toprule" valign="top"> <p class="First">8.2</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">8.1</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" valign="top"> <p class="First">-1.1</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-0.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> Difference from exenatide arm (adjusted mean)<span class="Sup"> b</span> </p> <p> 95% Confidence Interval</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">-0.3**</p> <p>(-0.5, -0.2)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Percentage of patients achieving HbA<span class="Sub">1c</span> &lt;7%</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">54</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">43</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Fasting Plasma Glucose (mg/dL) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="top"> <p class="First"> Baseline</p> </td><td align="center" class="Toprule" valign="top"> <p class="First">176</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">171</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" valign="top"> <p class="First">-29</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-11</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> Difference from exenatide arm (adjusted mean)<span class="Sup"> b</span> </p> <p> 95% Confidence Interval</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-18**</p> <p>(-25, -12)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> </tbody> </table></div>

aIntent-to-treat population using last observation carried forward

bLeast squares mean adjusted for baseline value

**p-value <0.0001

Add-on to Metformin and Thiazolidinedione

In this 26-week trial, 533 adult patients with type 2 diabetes mellitus were randomized to VICTOZA 1.2 mg, VICTOZA 1.8 mg or placebo, all as add-on to rosiglitazone (8 mg) plus metformin (2,000 mg). Patients underwent a 9 week run-in period (3-week forced dose escalation followed by a 6-week dose maintenance phase) with rosiglitazone (starting at 4 mg and increasing to 8 mg/day within 2 weeks) and metformin (starting at 500 mg with increasing weekly increments of 500 mg to a final dose of 2,000 mg/day). Only patients who tolerated the final dose of rosiglitazone (8 mg/day) and metformin (2000 mg/day) and completed the 6-week dose maintenance phase were eligible for randomization into the trial.

The mean age of participants was 55 years, and the mean duration of diabetes was 9 years. Participants were 61.6% male, 84.2% White, 10.2% Black or African American and 16.4% of Hispanic or Latino ethnicity. The mean BMI was 33.9 kg/m2.

Treatment with VICTOZA as add-on to metformin and rosiglitazone produced a statistically significant reduction in mean HbA1c compared to placebo add-on to metformin and rosiglitazone (Table 10). The percentage of patients who discontinued due to ineffective therapy was 1.7% in the VICTOZA 1.8 mg + metformin + rosiglitazone treatment group, 1.7% in the VICTOZA 1.2 mg + metformin + rosiglitazone treatment group, and 16.4% in the placebo + metformin + rosiglitazone treatment group.

Table 10. Results of a 26-week Trial of VICTOZA as Add-on to Metformin and Thiazolidinedione in Adult Patients with Type 2 Diabetes Mellitusa

<div class="scrollingtable"><table width="99.54%"> <col width="52%"/> <col width="14%"/> <col width="14%"/> <col width="20%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">VICTOZA </span> </p> <p> <span class="Bold">1.8 mg</span> +</p> <p> <span class="Bold">Metformin +</span> </p> <p> <span class="Bold">Rosiglitazone</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">VICTOZA </span> </p> <p> <span class="Bold">1.2 mg</span> +</p> <p> <span class="Bold">Metformin +</span> </p> <p> <span class="Bold">Rosiglitazone</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Placebo + Metformin +</span> </p> <dl> <dt> </dt> <dd> <span class="Bold">Rosiglitazone</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Intent-to-Treat Population (N)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">178</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">177</p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>175</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">HbA<span class="Sub">1c</span> (%) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="top"> <p class="First"> Baseline</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">8.6</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">8.5</p> </td><td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>8.4</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-1.5</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-1.5</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>-0.5</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> Difference from placebo + metformin + rosiglitazone arm (adjusted mean)<span class="Sup"> b</span> </dd> </dl> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-0.9**</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-0.9**</p> </td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> 95% Confidence Interval</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-1.1, -0.8)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-1.1, -0.8)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Percentage of patients achieving HbA<span class="Sub">1c</span> &lt;7%</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">54</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">57</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>28</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Fasting Plasma Glucose (mg/dL) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="top"> <p class="First"> Baseline</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">185</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">181</p> </td><td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>179</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-44</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-40 </p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>-8 </dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> Difference from placebo + metformin + rosiglitazone arm (adjusted mean)<span class="Sup"> b</span> </dd> </dl> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-36**</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-32**</p> </td><td class="Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> 95% Confidence Interval</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-44, -27)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-41, -23)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Body Weight (kg) (Mean)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="top"> <p class="First"> Baseline</p> </td><td align="center" class="Rrule Toprule" valign="top"> <p class="First">94.9</p> </td><td align="center" class="Lrule Rrule Toprule" valign="top"> <p class="First">95.3</p> </td><td class="Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>98.5</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> Change from baseline (adjusted mean)<span class="Sup"> b</span> </p> </td><td align="center" class="Rrule" valign="top"> <p class="First">-2.0</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-1.0</p> </td><td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>+0.6</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> Difference from placebo + metformin + rosiglitazone arm (adjusted mean)<span class="Sup"> b</span> </dd> </dl> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-2.6**</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-1.6**</p> </td><td class="Lrule Rrule" valign="top"></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd> 95% Confidence Interval</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-3.4, -1.8)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">(-2.4, -1.0)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> </tbody> </table></div>

aIntent-to-treat population using last observation on study

bLeast squares mean adjusted for baseline value

**p-value <0.0001

VICTOZA Compared to Placebo Both With or Without metformin and/or Sulfonylurea and/or Pioglitazone and/or Basal or Premix insulin in Patients with Type 2 Diabetes Mellitus and Moderate Renal Impairment

In this 26-week, double-blind, randomized, placebo-controlled, parallel-group trial in adult patients with type 2 diabetes mellitus, 279 patients with moderate renal impairment, as per MDRD formula (eGFR 30−59 mL/min/1.73 m2), were randomized to VICTOZA or placebo once daily. VICTOZA was added to the patient’s stable pre-trial antidiabetic regimen (insulin therapy and/or metformin, pioglitazone, or sulfonylurea). The dose of VICTOZA was escalated according to approved labeling to achieve a dose of 1.8 mg per day. The insulin dose was reduced by 20% at randomization for patients with baseline HbA1c ≤ 8% and fixed until liraglutide dose escalation was complete. Dose reduction of insulin and SU was allowed in case of hypoglycemia; up titration of insulin was allowed but not beyond the pre-trial dose.

The mean age of participants was 67 years, and the mean duration of diabetes was 15 years. Participants were 50.5% male, 92.3% White, 6.6% Black or African American, and 7.2% of Hispanic or Latino ethnicity. The mean BMI was 33.9 kg/m2. Approximately half of patients had an eGFR between 30 and <45mL/min/1.73 m2.

Treatment with VICTOZA resulted in a statistically significant reduction in HbA1c from baseline at Week 26 compared to placebo (see Table 11). 123 patients reached the 1.8 mg dose of VICTOZA.

Table 11. Results of a 26-week Trial of VICTOZA Compared to Placebo in Adult Patients with Type 2 Diabetes Mellitus and Moderate Renal Impairmenta

<div class="scrollingtable"><table width="100%"> <col width="36%"/> <col width="34%"/> <col width="30%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">VICTOZA 1.8 mg + insulin and/or OAD</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo + insulin and/or OAD</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Intent to Treat Population (N)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">140</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">137</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">HbA<span class="Sub">1c</span> (%)</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Baseline (mean)</p> </td><td align="center" valign="top"> <p class="First">8.1</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">8.0</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Change from baseline (estimated mean) <span class="Sup">b, c</span> </p> </td><td align="center" valign="top"> <p class="First">-0.9</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-0.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Difference from placebo<span class="Sup">b, c</span> </p> <p>95% Confidence Interval</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">-0.6*</p> <p>(-0.8, -0.3)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Proportion achieving HbA<span class="Sub">1c</span> &lt; 7% <span class="Sup">d</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">39.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">19.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">FPG (mg/dL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Baseline (mean)</p> </td><td align="center" valign="top"> <p class="First">171</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">167</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Change from baseline (estimated mean) <span class="Sup">e</span> </p> </td><td align="center" valign="top"> <p class="First">-22</p> </td><td align="center" class="Lrule Rrule" valign="top"> <p class="First">-10</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Difference from placebo<span class="Sup">e</span> </p> <p>95% Confidence Interval</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-12**</p> <p>(-23, -0.8)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> </tbody> </table></div>

a Intent-to-treat population

b Estimated using a mixed model for repeated measurement with treatment, country, stratification groups as factors and baseline as a covariate, all nested within visit. Multiple imputation method modeled “wash out” of the treatment effect for patients having missing data who discontinued treatment.

c Early treatment discontinuation, before week 26, occurred in 25% and 22% of VICTOZA and placebo patients, respectively.

d Based on the known number of subjects achieving HbA1c < 7%. When applying the multiple imputation method described in b) above, the estimated percents achieving HbA1c < 7% are 47.6% and 24.9% for VICTOZA and placebo, respectively.

e Estimated using a mixed model for repeated measurement with treatment, country, stratification groups as factors and baseline as a covariate, all nested within visit.

*p-value <0.0001

**p-value <0.05

VICTOZA was evaluated in a 26-week, double-blind, randomized, parallel group, placebo controlled multi-center trial (NCT01541215), in 134 pediatric patients with type 2 diabetes mellitus aged 10 years and older. Patients were randomized to VICTOZA once-daily or placebo once-daily in combination with metformin with or without basal insulin treatment. All patients were on a metformin dose of 1000 to 2000 mg prior to randomization. The basal insulin dose was decreased by 20% at randomization and VICTOZA was titrated weekly by 0.6 mg for 2 to 3 weeks based on tolerability and an average fasting plasma glucose goal of ≤110 mg/dL.

The mean age was 14.6 years: 29.9% were ages 10-14 years, and 70.1% were greater than 14 years of age. 38.1% were male, 64.9% were White, 13.4% were Asian, 11.9% were Black or African American; 29.1% were of Hispanic or Latino ethnicity. The mean BMI was 33.9 kg/m2 and the mean BMI SDS was 2.9. 18.7% of patients were using basal insulin at baseline. The mean duration of diabetes was 1.9 years and the mean HbA1c was 7.8%.

At week 26, treatment with VICTOZA was superior in reducing HbA1c from baseline versus placebo. The estimated treatment difference in HbA1c reduction from baseline between VICTOZA and placebo was -1.06% with a 95% confidence interval of [-1.65%; -0.46%] (see Table 12).

Table 12. Results at week 26 in a trial comparing VICTOZA in combination with metformin with or without basal insulin versus Placebo in combination with metformin with or without basal insulin in Pediatric Patients Aged 10 Years and Older with Type 2 Diabetes Mellitus

<div class="scrollingtable"><table width="100%"> <col width="34%"/> <col width="32%"/> <col width="33%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">VICTOZA+metformin±basal insulin </span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo+metformin±basal insulin</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">N</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">66</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">68</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">HbA<span class="Sub">1c</span> (%)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Baseline</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.9</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">End of 26 weeks </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Adjusted mean change from baseline after 26 weeks<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">-0.64</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">0.42</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Treatment difference [95% CI] </p> <p>VICTOZA vs Placebo</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"> <p class="First">-1.06 [-1.65; -0.46]*</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Percentage of patients achieving HbA<span class="Sub">1c</span> &lt;7%<span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">63.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">36.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">FPG (mg/dL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Baseline</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">157</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">147</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">End of 26 weeks</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">132</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">166</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Adjusted mean change from baseline after 26 weeks<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">-19.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">14.4</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Treatment difference [95% CI] </p> <p>VICTOZA vs Placebo</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"> <p class="First">-33.83 [-55.74 ; -11.92]</p> </td> </tr> </tbody> </table></div>

a The change from baseline to end of treatment visit in HbA1c and FPG was analyzed using a pattern mixture model with multiple imputation. Missing observations (10.6% in the VICTOZA, 14.5% in the placebo) were imputed from the placebo arm based on multiple (x10,000) imputations. The data for week 26 was then analyzed with an ANCOVA model containing treatment, sex and age group as fixed effects and baseline value as covariate.

b Categories are derived from continuous measurements of HbA1c using a pattern mixture model with multiple imputation for missing observations.

* p-value <0.001

The LEADER trial (NCT01179048) was a multi-national, multi-center, placebo-controlled, double-blind trial. In this study, 9,340 adult patients with inadequately controlled type 2 diabetes mellitus and atherosclerotic cardiovascular disease (CVD) were randomized to VICTOZA 1.8 mg or placebo for a median duration of 3.5 years. The study compared the risk of major adverse cardiovascular events between VICTOZA and placebo when these were added to, and used concomitantly with, background standard of care treatments for type 2 diabetes mellitus. The primary endpoint, major adverse cardiac events (MACE), was the time to first occurrence of a three part composite outcome which included; cardiovascular death, non-fatal myocardial infarction and non-fatal stroke.

Patients eligible to enter the trial were; 50 years of age or older and had established, stable, cardiovascular, cerebrovascular, peripheral artery disease, chronic kidney disease or New York Heart Association (NYHA) class II and III heart failure (80% of the enrolled population) or were 60 years of age or older and had other specified risk factors for cardiovascular disease (20% of the enrolled population).

At baseline, demographic and disease characteristics were balanced. The mean age was 64 years and the population was 64.3% male, 77.5% White, 10.0% Asian, and 8.3% Black or African American. In the study, 12.1% of the population identified as Hispanic or Latino ethnicity. The mean duration of type 2 diabetes mellitus was 12.8 years, the mean HbA1c was 8.7% and the mean BMI was 32.5 kg/m2. A history of previous myocardial infarction was reported in 31% of randomized individuals, a prior revascularization procedure in 39%, a prior ischemic stroke in 11%, documented symptomatic coronary disease in 9%, documented asymptomatic cardiac ischemia in 26%, and a diagnosis of NYHA class II to III heart failure in 14%. The mean eGFR at baseline was 79 mL/min/1.73 m2 and 41.8% of patients had mild renal impairment (eGFR 60 to 90 mL/min/1.73m2), 20.7% had moderate renal impairment (eGFR 30 to 60 mL/min/1.73m2) and 2.4% of patients had severe renal impairment (eGFR < 30 mL/min/1.73m2). 

At baseline, patients treated their diabetes with; diet and exercise only (3.9%), oral antidiabetic drugs only (51.5%), oral antidiabetic drugs and insulin (36.7%) or insulin only (7.9%). The most common background antidiabetic drugs used at baseline and in the trial were metformin, sulfonylurea and insulin. Use of DPP-4 inhibitors and other GLP-1 receptor agonists was excluded by protocol and sodium-glucose cotransporter-2 (SGLT-2) inhibitors were either not approved or not widely available. At baseline, cardiovascular disease and risk factors were managed with; non-diuretic antihypertensives (92.4%), diuretics (41.8%), statin therapy (72.1%) and platelet aggregation inhibitors (66.8%). During the trial, investigators could modify anti-diabetic and cardiovascular medications to achieve local standard of care treatment targets with respect to blood glucose, lipid, and blood pressure, and manage patients recovering from an acute coronary syndrome or stroke event per local treatment guidelines.

For the primary analysis, a Cox proportional hazards model was used to test for non-inferiority against the pre-specified risk margin of 1.3 for the hazard ratio of MACE and to test for superiority on MACE if non-inferiority was demonstrated. Type 1 error was controlled across multiple tests.

VICTOZA significantly reduced the occurrence of MACE. The estimated hazard ratio (95% CI) for time to first MACE was 0.87 (0.78, 0.97). Refer to Figure 5 and Table 13.

Vital status was available for 99.7% of subjects in the trial. A total of 828 deaths were recorded during the LEADER trial. A majority of the deaths in the trial were categorized as cardiovascular deaths and non-cardiovascular deaths were balanced between the treatment groups (3.5% in patients treated with VICTOZA and 3.6% in patients treated with placebo). The estimated hazard ratio of time to all-cause death for VICTOZA compared to placebo was 0.85 (0.74, 0.97).

Figure 5. Kaplan-Meier: Time to First Occurrence of a MACE in the LEADER Trial (Patients with Type 2 Diabetes Mellitus and Atherosclerotic CVD)

Table 13. Treatment Effect for the Primary Composite Endpoint, MACE, and its Components in the LEADER Trial (Patients with Type 2 Diabetes Mellitus and Atherosclerotic CVD)a

<div class="scrollingtable"><table width="100%"> <col width="49%"/> <col width="17%"/> <col width="16%"/> <col width="19%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">VICTOZA</span> </p> <p> <span class="Bold">N=4668</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">N=4672</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Hazard Ratio </span> </p> <p> <span class="Bold">(95% CI)<span class="Sup">b</span></span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke (MACE)</p> <p>(time to first occurrence)<span class="Sup"> c</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">608 (13.0%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">694 (14.9%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.87 (0.78; 0.97)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Non-fatal myocardial infarction<span class="Sup">d</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">281 (6.0%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">317 (6.8%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.88 (0.75;1.03)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Non-fatal stroke<span class="Sup">d</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">159 (3.4%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">177 (3.8%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.89 (0.72;1.11)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Cardiovascular death<span class="Sup">d</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">219 (4.7%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">278 (6%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.78 (0.66;0.93)</p> </td> </tr> </tbody> </table></div>

aFull analysis set (all randomized patients)

bCox-proportional hazards model with treatment as a factor

cp-value for superiority (2-sided) 0.011

dNumber and percentage of first events

{ "type": "", "children": [], "text": "" }

VICTOZA Injection: 18 mg/3 mL (6 mg/mL) clear, colorless solution in a pre-filled, single-patient-use pen that delivers doses of 0.6 mg, 1.2 mg, or 1.8 mg is available in the following package sizes:

{ "type": "p", "children": [], "text": "VICTOZA Injection: 18 mg/3 mL (6 mg/mL) clear, colorless solution in a pre-filled, single-patient-use pen that delivers doses of 0.6 mg, 1.2 mg, or 1.8 mg is available in the following package sizes: " }

{ "type": "", "children": [], "text": "" }

Prior to first use, VICTOZA should be stored in a refrigerator between 36ºF to 46ºF (2ºC to 8ºC). Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze VICTOZA and do not use VICTOZA if it has been frozen.

{ "type": "p", "children": [], "text": "Prior to first use, VICTOZA should be stored in a refrigerator between 36ºF to 46ºF (2ºC to 8ºC). Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze VICTOZA and do not use VICTOZA if it has been frozen." }

After first use of the VICTOZA pen, the pen can be stored for 30 days at controlled room temperature (59°F to 86°F; 15°C to 30°C) or in a refrigerator (36°F to 46°F; 2°C to 8°C). Keep the pen cap on when not in use. Protect VICTOZA from excessive heat and sunlight. Always remove and safely discard the needle after each injection and store the VICTOZA pen without an injection needle attached. This will reduce the potential for contamination, infection, and leakage while also ensuring dosing accuracy. Always use a new needle for each injection to prevent contamination.

{ "type": "p", "children": [], "text": "After first use of the VICTOZA pen, the pen can be stored for 30 days at controlled room temperature (59°F to 86°F; 15°C to 30°C) or in a refrigerator (36°F to 46°F; 2°C to 8°C). Keep the pen cap on when not in use. Protect VICTOZA from excessive heat and sunlight. Always remove and safely discard the needle after each injection and store the VICTOZA pen without an injection needle attached. This will reduce the potential for contamination, infection, and leakage while also ensuring dosing accuracy. Always use a new needle for each injection to prevent contamination." }

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Medication Guide)." }

Risk of Thyroid C-cell Tumors

{ "type": "p", "children": [], "text": "\nRisk of Thyroid C-cell Tumors\n" }

Inform patients that liraglutide causes benign and malignant thyroid C-cell tumors in mice and rats and that the human relevance of this finding is unknown. Counsel patients to report symptoms of thyroid tumors (e.g., a lump in the neck, hoarseness, dysphagia, or dyspnea) to their physician [see Boxed Warning and Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Inform patients that liraglutide causes benign and malignant thyroid C-cell tumors in mice and rats and that the human relevance of this finding is unknown. Counsel patients to report symptoms of thyroid tumors (e.g., a lump in the neck, hoarseness, dysphagia, or dyspnea) to their physician [see Boxed Warning and Warnings and Precautions (5.1)]. " }

Acute Pancreatitis

{ "type": "p", "children": [], "text": "\nAcute Pancreatitis\n" }

Inform patients of the potential risk for acute pancreatitis and its symptoms: severe abdominal pain that may

{ "type": "p", "children": [], "text": "Inform patients of the potential risk for acute pancreatitis and its symptoms: severe abdominal pain that may" }

radiate to the back, and which may or may not be accompanied by vomiting. Instruct patients to discontinue

{ "type": "p", "children": [], "text": "radiate to the back, and which may or may not be accompanied by vomiting. Instruct patients to discontinue" }

VICTOZA promptly and contact their physician if pancreatitis is suspected [see Warnings and Precautions

{ "type": "p", "children": [], "text": "VICTOZA promptly and contact their physician if pancreatitis is suspected [see Warnings and Precautions\n" }

(5.2)].

{ "type": "p", "children": [], "text": "\n(5.2)].\n" }

Never Share a VICTOZA Pen Between Patients

{ "type": "p", "children": [], "text": "\nNever Share a VICTOZA Pen Between Patients\n" }

Advise patients that they must never share a VICTOZA pen with another person, even if the needle is changed, because doing so carries a risk for transmission of blood-borne pathogens [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Advise patients that they must never share a VICTOZA pen with another person, even if the needle is changed, because doing so carries a risk for transmission of blood-borne pathogens [see Warnings and Precautions (5.3)]." }

Hypoglycemia

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Inform patients that hypoglycemia has been reported when VICTOZA is used with insulin secretagogues or insulin and may occur in pediatric patients regardless of concomitant antidiabetic treatment. Educate patients or caregivers on the signs and symptoms of hypoglycemia [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "Inform patients that hypoglycemia has been reported when VICTOZA is used with insulin secretagogues or insulin and may occur in pediatric patients regardless of concomitant antidiabetic treatment. Educate patients or caregivers on the signs and symptoms of hypoglycemia [see Warnings and Precautions (5.4)]. " }

Acute Kidney Injury Due to Volume Depletion

{ "type": "p", "children": [], "text": "\nAcute Kidney Injury Due to Volume Depletion\n" }

Inform patients of the potential risk of acute kidney injury due to dehydration associated with gastrointestinal

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adverse reactions. Advise patients to take precautions to avoid fluid depletion. Inform patients of the signs and symptoms of acute kidney injury and instruct them to promptly report any of these signs or symptoms or

{ "type": "p", "children": [], "text": "adverse reactions. Advise patients to take precautions to avoid fluid depletion. Inform patients of the signs and symptoms of acute kidney injury and instruct them to promptly report any of these signs or symptoms or" }

persistent (or extended) nausea, vomiting, and diarrhea to their healthcare provider [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "persistent (or extended) nausea, vomiting, and diarrhea to their healthcare provider [see Warnings and Precautions (5.5)]." }

Severe Gastrointestinal Adverse Reactions

{ "type": "p", "children": [], "text": "\nSevere Gastrointestinal Adverse Reactions\n" }

Inform patients of the potential risk of severe gastrointestinal adverse reactions. Instruct patients to contact their healthcare provider if they have severe or persistent gastrointestinal symptoms [see Warnings and Precautions

{ "type": "p", "children": [], "text": "Inform patients of the potential risk of severe gastrointestinal adverse reactions. Instruct patients to contact their healthcare provider if they have severe or persistent gastrointestinal symptoms [see Warnings and Precautions\n" }

(5.6)].

{ "type": "p", "children": [], "text": "\n(5.6)].\n" }

Hypersensitivity Reactions

{ "type": "p", "children": [], "text": "\nHypersensitivity Reactions\n" }

Inform patients that serious hypersensitivity reactions have been reported during postmarketing use of VICTOZA. Advise patients on the symptoms of hypersensitivity reactions and instruct them to stop taking VICTOZA and seek medical advice promptly if such symptoms occur [see Warnings and Precautions (5.7)].

{ "type": "p", "children": [], "text": "Inform patients that serious hypersensitivity reactions have been reported during postmarketing use of VICTOZA. Advise patients on the symptoms of hypersensitivity reactions and instruct them to stop taking VICTOZA and seek medical advice promptly if such symptoms occur [see Warnings and Precautions (5.7)]." }

Acute Gallbladder Disease

{ "type": "p", "children": [], "text": "\nAcute Gallbladder Disease \n" }

Inform patients of the potential risk for cholelithiasis or cholecystitis. Instruct patients to contact their physician if cholelithiasis or cholecystitis is suspected for appropriate clinical follow-up [see Warnings and Precautions (5.8)].

{ "type": "p", "children": [], "text": "Inform patients of the potential risk for cholelithiasis or cholecystitis. Instruct patients to contact their physician if cholelithiasis or cholecystitis is suspected for appropriate clinical follow-up [see Warnings and Precautions (5.8)]." }

Pulmonary Aspiration During General Anesthesia or Deep Sedation

{ "type": "p", "children": [], "text": "\nPulmonary Aspiration During General Anesthesia or Deep Sedation \n" }

Inform patients that VICTOZA may cause their stomach to empty more slowly which may lead to complications with anesthesia or deep sedation during planned surgeries or procedures. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking VICTOZA [see Warnings and Precautions (5.9)].

{ "type": "p", "children": [], "text": "Inform patients that VICTOZA may cause their stomach to empty more slowly which may lead to complications with anesthesia or deep sedation during planned surgeries or procedures. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking VICTOZA [see Warnings and Precautions (5.9)].\n" }

Missed Dose

{ "type": "p", "children": [], "text": "\nMissed Dose\n" }

Inform patients not to take an extra dose of VICTOZA to make up for a missed dose. If a dose is missed, the once-daily regimen should be resumed as prescribed with the next scheduled dose. If more than 3 days have elapsed since the last dose, advise the patient to reinitiate VICTOZA at 0.6 mg to mitigate any gastrointestinal symptoms associated with reinitiation of treatment. VICTOZA should be titrated at the discretion of the healthcare provider [see Dosage and Administration (2.2)].

{ "type": "p", "children": [], "text": "Inform patients not to take an extra dose of VICTOZA to make up for a missed dose. If a dose is missed, the once-daily regimen should be resumed as prescribed with the next scheduled dose. If more than 3 days have elapsed since the last dose, advise the patient to reinitiate VICTOZA at 0.6 mg to mitigate any gastrointestinal symptoms associated with reinitiation of treatment. VICTOZA should be titrated at the discretion of the healthcare provider [see Dosage and Administration (2.2)].\n" }

Manufactured by:

{ "type": "p", "children": [], "text": "Manufactured by:" }

Novo Nordisk A/S

{ "type": "p", "children": [], "text": "Novo Nordisk A/S" }

DK-2880 Bagsvaerd, Denmark

{ "type": "p", "children": [], "text": "DK-2880 Bagsvaerd, Denmark" }

VICTOZA® is a registered trademark of Novo Nordisk A/S.

{ "type": "p", "children": [], "text": "VICTOZA® is a registered trademark of Novo Nordisk A/S." }

PATENTInformation: http://novonordisk-us.com/products/product-patents.html

{ "type": "p", "children": [], "text": "\nPATENTInformation: http://novonordisk-us.com/products/product-patents.html\n" }

© 2025 Novo Nordisk

{ "type": "p", "children": [], "text": "© 2025 Novo Nordisk" }

For information about VICTOZA contact:

{ "type": "p", "children": [], "text": "For information about VICTOZA contact:" }

Novo Nordisk Inc.

{ "type": "p", "children": [], "text": "Novo Nordisk Inc." }

800 Scudders Mill Road

{ "type": "p", "children": [], "text": "800 Scudders Mill Road" }

Plainsboro, NJ 08536

{ "type": "p", "children": [], "text": "Plainsboro, NJ 08536" }

1-877-484-2869

{ "type": "p", "children": [], "text": "1-877-484-2869" }

<div class="scrollingtable"><table width="100%"> <col width="33%"/> <col width="17%"/> <col width="17%"/> <col width="33%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="4" valign="top"> <p class="First"> <span class="Bold">VICTOZA<span class="Sup">®</span> (VIC-tow-za)</span> <br/> <span class="Bold">(liraglutide) injection, for subcutaneous use</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First">Read this Medication Guide before you start using VICTOZA and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">What is the most important information I should know about VICTOZA?</span> <br/> <span class="Bold">VICTOZA may cause serious side effects, including:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Possible thyroid tumors, including cancer</span>. Tell your healthcare provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. In studies with rats and mice, VICTOZA and medicines that work like VICTOZA caused thyroid tumors, including thyroid cancer. It is not known if VICTOZA will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people.</dd> <dt>•</dt> <dd>Do not use VICTOZA if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC), or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">What is VICTOZA?</span> </p> <p>VICTOZA is an injectable prescription medicine used: </p> <dl> <dt>•</dt> <dd>along with diet and exercise to improve blood sugar (glucose) in adults and children who are 10 years of age and older with type 2 diabetes mellitus.</dd> <dt>•</dt> <dd>to reduce the risk of major cardiovascular events such as heart attack, stroke or death in adults with type 2 diabetes mellitus with known heart disease.</dd> <dt>•</dt> <dd>VICTOZA is not recommended for people who take liraglutide or other medicines called glucagon-like peptide-1 (GLP-1) receptor agonists. </dd> <dt>•</dt> <dd>It is not known if VICTOZA is safe and effective to lower blood sugar (glucose) in children under 10 years of age.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">Who should not use VICTOZA?</span> <br/> <span class="Bold">Do not use VICTOZA if:</span> </p> <dl> <dt>•</dt> <dd>you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC) or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).</dd> <dt>•</dt> <dd>you have had a serious allergic reaction to liraglutide or any of the ingredients in VICTOZA. See the end of this Medication Guide for a complete list of ingredients in VICTOZA. See “<span class="Bold">What are the possible side effects of VICTOZA?</span>” for symptoms of a serious allergic reaction. </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">What should I tell my healthcare provider before using VICTOZA?</span> <br/> <span class="Bold">Before using VICTOZA, tell your healthcare provider if you have any other medical conditions, including if you:</span> </p> <dl> <dt>•</dt> <dd>have or have had problems with your pancreas.</dd> <dt>•</dt> <dd>have severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems with digesting food.</dd> <dt>•</dt> <dd>are scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation).</dd> <dt>•</dt> <dd>are pregnant or plan to become pregnant. It is not known if VICTOZA will harm your unborn baby. Tell your healthcare provider if you become pregnant while using VICTOZA.</dd> <dt>•</dt> <dd>are breastfeeding or plan to breastfeed. It is not known if VICTOZA passes into your breast milk. You should talk with your healthcare provider about the best way to feed your baby while using VICTOZA. </dd> </dl> <p> <span class="Bold">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements. VICTOZA may affect the way some medicines work and some medicines may affect the way VICTOZA works. </p> <p> <span class="Bold">Before using VICTOZA, talk to your healthcare provider about low blood sugar and how to manage it.</span> Tell your healthcare provider if you are taking other medicines to treat diabetes, including insulin or sulfonylureas.</p> <p>Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">How should I use VICTOZA?</span> </p> <dl> <dt>•</dt> <dd>Read the <span class="Bold">Instructions for Use</span> that comes with VICTOZA.</dd> <dt>•</dt> <dd>Use VICTOZA exactly as your healthcare provider tells you to. </dd> <dt>•</dt> <dd> <span class="Bold">Your healthcare provider should show you how to use VICTOZA before you use it for the first time.</span> </dd> <dt>•</dt> <dd>Inject your dose of VICTOZA under the skin (subcutaneously) of your stomach (abdomen), thigh, or upper arm. <span class="Bold">Do not </span>inject VICTOZA into a muscle (intramuscularly) or vein (intravenously).</dd> <dt>•</dt> <dd> <span class="Bold">Use VICTOZA 1 time each day, at any time of the day.</span> </dd> <dt>•</dt> <dd>If you miss a dose of VICTOZA, take the missed dose at the next scheduled dose. <span class="Bold">Do not </span>take 2 doses of VICTOZA at the same time</dd> <dt>•</dt> <dd>VICTOZA may be taken with or without food.</dd> <dt>•</dt> <dd> <span class="Bold">Do not </span>mix insulin and VICTOZA together in the same injection.</dd> <dt>•</dt> <dd>You may give an injection of VICTOZA and insulin in the same body area (such as your stomach area), but not right next to each other.</dd> <dt>•</dt> <dd>Change (rotate) your injection site with each injection. <span class="Bold">Do not</span> use the same site for each injection.</dd> <dt>•</dt> <dd> <span class="Bold">Do not share your VICTOZA pen with other people, even if the needle has been changed. </span>You may give other people a serious infection or get a serious infection from them.</dd> <dt>•</dt> <dd>If you take too much VICTOZA, call your healthcare provider or the Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away. </dd> <dt>•</dt> <dd>The VICTOZA pen you are using should be thrown away 30 days after you start using it.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">What are the possible side effects of VICTOZA?</span> <br/> <span class="Bold">VICTOZA may cause serious side effects, including:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">See “What is the most important information I should know about VICTOZA?”</span> </dd> <dt>•</dt> <dd> <span class="Bold">inflammation of your pancreas (pancreatitis). </span>Stop using VICTOZA and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back. </dd> <dt>•</dt> <dd> <span class="Bold">low blood sugar (hypoglycemia).</span> Your risk for getting low blood sugar may be higher if you use VICTOZA with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin. In children who are 10 years of age and older, the risk for low blood sugar may be higher with VICTOZA regardless of use with another medicine that can also lower blood sugar. </dd> <dt> </dt> <dd> <span class="Bold">Signs and symptoms of low blood sugar may include:</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Toprule" valign="top"> <dl> <dt>o</dt> <dd>dizziness or light-headedness</dd> <dt>o</dt> <dd>sweating</dd> <dt>o</dt> <dd>confusion or drowsiness</dd> <dt>o</dt> <dd>headache</dd> </dl> </td><td class="Botrule Toprule" colspan="2" valign="top"> <dl> <dt>o</dt> <dd>blurred vision</dd> <dt>o</dt> <dd>slurred speech</dd> <dt>o</dt> <dd>shakiness</dd> <dt>o</dt> <dd>fast heartbeat</dd> </dl> </td><td class="Botrule Rrule Toprule" valign="top"> <dl> <dt>o</dt> <dd>anxiety, irritability, or mood changes</dd> <dt>o</dt> <dd>hunger</dd> <dt>o</dt> <dd>weakness</dd> <dt>o</dt> <dd>feeling jittery</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="4" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">dehydration leading to kidney problems. </span>Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration) which may cause kidney problems. It is important for you to drink fluids to help reduce your chance of dehydration. Tell your healthcare provider right away if you have nausea, vomiting, or diarrhea that does not go away.</dd> <dt>•</dt> <dd> <span class="Bold">severe stomach problems.</span> Stomach problems, sometimes severe, have been reported in people who use VICTOZA. Tell your healthcare provider if you have stomach problems that are severe or will not go away.</dd> <dt>•</dt> <dd> <span class="Bold">serious allergic reactions.</span> Stop using VICTOZA and get medical help right away if you have any symptoms of a serious allergic reaction including:</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Toprule" colspan="2" valign="top"> <dl> <dt>o</dt> <dd>swelling of your face, lips, tongue or throat</dd> <dt>o</dt> <dd>problems breathing or swallowing</dd> <dt>o</dt> <dd>severe rash or itching</dd> </dl> </td><td class="Botrule Rrule Toprule" colspan="2" valign="top"> <dl> <dt>o</dt> <dd>fainting or feeling dizzy</dd> <dt>o</dt> <dd>very rapid heartbeat</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="4" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">gallbladder problems.</span> Gallbladder problems have happened in some people who take VICTOZA. Tell your healthcare provider right away if you get symptoms of gallbladder problems which may include:</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Toprule" colspan="2" valign="top"> <dl> <dt>o</dt> <dd>pain in your upper stomach (abdomen)</dd> <dt>o</dt> <dd>fever</dd> </dl> </td><td class="Botrule Rrule Toprule" colspan="2" valign="top"> <dl> <dt>o</dt> <dd>yellowing of skin or eyes (jaundice)</dd> <dt>o</dt> <dd>clay-colored stools</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="4" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">food or liquid getting into the lungs during surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). </span>VICTOZA may increase the chance of food getting into your lungs during surgery or other procedures. Tell all your healthcare providers that you are taking VICTOZA before you are scheduled to have surgery or other procedures.</dd> </dl> <p class="First"> <span class="Bold">The most common side effects of VICTOZA may include</span> nausea, diarrhea, vomiting, decreased appetite, indigestion and constipation.</p> <p>Talk to your healthcare provider about any side effect that bothers you or does not go away. </p> <p>These are not all the possible side effects of VICTOZA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">General information about the safe and effective use of VICTOZA.</span> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use VICTOZA for a condition for which it was not prescribed. Do not give VICTOZA to other people, even if they have the same symptoms that you have. It may harm them. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about VICTOZA that is written for health professionals.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">What are the ingredients in VICTOZA?</span> <br/> <span class="Bold">Active ingredient:</span> liraglutide<br/> <span class="Bold">Inactive ingredients: </span>disodium phosphate dihydrate, propylene glycol, phenol and water for injection. Hydrochloric acid or sodium hydroxide may be added to adjust pH </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First">Manufactured by: Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark</p> <p> <span class="Italics">Victoza<span class="Sup">®</span> is a registered trademark of Novo Nordisk A/S.</span> </p> <p>For more information, go to victoza.com or call 1-877-484-2869.</p> <p>PATENT Information: <a href="http://novonordisk-us.com/patients/products/product-patents.html">http://novonordisk-us.com/patients/products/product-patents.html</a> </p> <p>© 2025 Novo Nordisk </p> <p>This Medication Guide has been approved by the U.S. Food and Drug Administration. </p> <p>Revised: 05/2025</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"33%\"/>\n<col width=\"17%\"/>\n<col width=\"17%\"/>\n<col width=\"33%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">VICTOZA<span class=\"Sup\">®</span> (VIC-tow-za)</span>\n<br/>\n<span class=\"Bold\">(liraglutide) injection, for subcutaneous use</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">Read this Medication Guide before you start using VICTOZA and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information I should know about VICTOZA?</span>\n<br/>\n<span class=\"Bold\">VICTOZA may cause serious side effects, including:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Possible thyroid tumors, including cancer</span>. Tell your healthcare provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. In studies with rats and mice, VICTOZA and medicines that work like VICTOZA caused thyroid tumors, including thyroid cancer. It is not known if VICTOZA will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people.</dd>\n<dt>•</dt>\n<dd>Do not use VICTOZA if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC), or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is VICTOZA?</span>\n</p>\n<p>VICTOZA is an injectable prescription medicine used: </p>\n<dl>\n<dt>•</dt>\n<dd>along with diet and exercise to improve blood sugar (glucose) in adults and children who are 10 years of age and older with type 2 diabetes mellitus.</dd>\n<dt>•</dt>\n<dd>to reduce the risk of major cardiovascular events such as heart attack, stroke or death in adults with type 2 diabetes mellitus with known heart disease.</dd>\n<dt>•</dt>\n<dd>VICTOZA is not recommended for people who take liraglutide or other medicines called glucagon-like peptide-1 (GLP-1) receptor agonists. </dd>\n<dt>•</dt>\n<dd>It is not known if VICTOZA is safe and effective to lower blood sugar (glucose) in children under 10 years of age.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Who should not use VICTOZA?</span>\n<br/>\n<span class=\"Bold\">Do not use VICTOZA if:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC) or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).</dd>\n<dt>•</dt>\n<dd>you have had a serious allergic reaction to liraglutide or any of the ingredients in VICTOZA. See the end of this Medication Guide for a complete list of ingredients in VICTOZA. See “<span class=\"Bold\">What are the possible side effects of VICTOZA?</span>” for symptoms of a serious allergic reaction. </dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What should I tell my healthcare provider before using VICTOZA?</span>\n<br/>\n<span class=\"Bold\">Before using VICTOZA, tell your healthcare provider if you have any other medical conditions, including if you:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>have or have had problems with your pancreas.</dd>\n<dt>•</dt>\n<dd>have severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems with digesting food.</dd>\n<dt>•</dt>\n<dd>are scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation).</dd>\n<dt>•</dt>\n<dd>are pregnant or plan to become pregnant. It is not known if VICTOZA will harm your unborn baby. Tell your healthcare provider if you become pregnant while using VICTOZA.</dd>\n<dt>•</dt>\n<dd>are breastfeeding or plan to breastfeed. It is not known if VICTOZA passes into your breast milk. You should talk with your healthcare provider about the best way to feed your baby while using VICTOZA. </dd>\n</dl>\n<p>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements. VICTOZA may affect the way some medicines work and some medicines may affect the way VICTOZA works. </p>\n<p>\n<span class=\"Bold\">Before using VICTOZA, talk to your healthcare provider about low blood sugar and how to manage it.</span> Tell your healthcare provider if you are taking other medicines to treat diabetes, including insulin or sulfonylureas.</p>\n<p>Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I use VICTOZA?</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Read the <span class=\"Bold\">Instructions for Use</span> that comes with VICTOZA.</dd>\n<dt>•</dt>\n<dd>Use VICTOZA exactly as your healthcare provider tells you to. </dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Your healthcare provider should show you how to use VICTOZA before you use it for the first time.</span>\n</dd>\n<dt>•</dt>\n<dd>Inject your dose of VICTOZA under the skin (subcutaneously) of your stomach (abdomen), thigh, or upper arm. <span class=\"Bold\">Do not </span>inject VICTOZA into a muscle (intramuscularly) or vein (intravenously).</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Use VICTOZA 1 time each day, at any time of the day.</span>\n</dd>\n<dt>•</dt>\n<dd>If you miss a dose of VICTOZA, take the missed dose at the next scheduled dose. <span class=\"Bold\">Do not </span>take 2 doses of VICTOZA at the same time</dd>\n<dt>•</dt>\n<dd>VICTOZA may be taken with or without food.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not </span>mix insulin and VICTOZA together in the same injection.</dd>\n<dt>•</dt>\n<dd>You may give an injection of VICTOZA and insulin in the same body area (such as your stomach area), but not right next to each other.</dd>\n<dt>•</dt>\n<dd>Change (rotate) your injection site with each injection. <span class=\"Bold\">Do not</span> use the same site for each injection.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not share your VICTOZA pen with other people, even if the needle has been changed. </span>You may give other people a serious infection or get a serious infection from them.</dd>\n<dt>•</dt>\n<dd>If you take too much VICTOZA, call your healthcare provider or the Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away. </dd>\n<dt>•</dt>\n<dd>The VICTOZA pen you are using should be thrown away 30 days after you start using it.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of VICTOZA?</span>\n<br/>\n<span class=\"Bold\">VICTOZA may cause serious side effects, including:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">See “What is the most important information I should know about VICTOZA?”</span>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">inflammation of your pancreas (pancreatitis). </span>Stop using VICTOZA and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back. </dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">low blood sugar (hypoglycemia).</span> Your risk for getting low blood sugar may be higher if you use VICTOZA with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin. In children who are 10 years of age and older, the risk for low blood sugar may be higher with VICTOZA regardless of use with another medicine that can also lower blood sugar. </dd>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Signs and symptoms of low blood sugar may include:</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Toprule\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>dizziness or light-headedness</dd>\n<dt>o</dt>\n<dd>sweating</dd>\n<dt>o</dt>\n<dd>confusion or drowsiness</dd>\n<dt>o</dt>\n<dd>headache</dd>\n</dl>\n</td><td class=\"Botrule Toprule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>blurred vision</dd>\n<dt>o</dt>\n<dd>slurred speech</dd>\n<dt>o</dt>\n<dd>shakiness</dd>\n<dt>o</dt>\n<dd>fast heartbeat</dd>\n</dl>\n</td><td class=\"Botrule Rrule Toprule\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>anxiety, irritability, or mood changes</dd>\n<dt>o</dt>\n<dd>hunger</dd>\n<dt>o</dt>\n<dd>weakness</dd>\n<dt>o</dt>\n<dd>feeling jittery</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"4\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">dehydration leading to kidney problems. </span>Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration) which may cause kidney problems. It is important for you to drink fluids to help reduce your chance of dehydration. Tell your healthcare provider right away if you have nausea, vomiting, or diarrhea that does not go away.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">severe stomach problems.</span> Stomach problems, sometimes severe, have been reported in people who use VICTOZA. Tell your healthcare provider if you have stomach problems that are severe or will not go away.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">serious allergic reactions.</span> Stop using VICTOZA and get medical help right away if you have any symptoms of a serious allergic reaction including:</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Toprule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>swelling of your face, lips, tongue or throat</dd>\n<dt>o</dt>\n<dd>problems breathing or swallowing</dd>\n<dt>o</dt>\n<dd>severe rash or itching</dd>\n</dl>\n</td><td class=\"Botrule Rrule Toprule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>fainting or feeling dizzy</dd>\n<dt>o</dt>\n<dd>very rapid heartbeat</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"4\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">gallbladder problems.</span> Gallbladder problems have happened in some people who take VICTOZA. Tell your healthcare provider right away if you get symptoms of gallbladder problems which may include:</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Toprule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>pain in your upper stomach (abdomen)</dd>\n<dt>o</dt>\n<dd>fever</dd>\n</dl>\n</td><td class=\"Botrule Rrule Toprule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>yellowing of skin or eyes (jaundice)</dd>\n<dt>o</dt>\n<dd>clay-colored stools</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"4\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">food or liquid getting into the lungs during surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). </span>VICTOZA may increase the chance of food getting into your lungs during surgery or other procedures. Tell all your healthcare providers that you are taking VICTOZA before you are scheduled to have surgery or other procedures.</dd>\n</dl>\n<p class=\"First\">\n<span class=\"Bold\">The most common side effects of VICTOZA may include</span> nausea, diarrhea, vomiting, decreased appetite, indigestion and constipation.</p>\n<p>Talk to your healthcare provider about any side effect that bothers you or does not go away. </p>\n<p>These are not all the possible side effects of VICTOZA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of VICTOZA.</span>\n</p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use VICTOZA for a condition for which it was not prescribed. Do not give VICTOZA to other people, even if they have the same symptoms that you have. It may harm them. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about VICTOZA that is written for health professionals.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in VICTOZA?</span>\n<br/>\n<span class=\"Bold\">Active ingredient:</span> liraglutide<br/>\n<span class=\"Bold\">Inactive ingredients: </span>disodium phosphate dihydrate, propylene glycol, phenol and water for injection. Hydrochloric acid or sodium hydroxide may be added to adjust pH </p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">Manufactured by: Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark</p>\n<p>\n<span class=\"Italics\">Victoza<span class=\"Sup\">®</span> is a registered trademark of Novo Nordisk A/S.</span>\n</p>\n<p>For more information, go to victoza.com or call 1-877-484-2869.</p>\n<p>PATENT Information: <a href=\"http://novonordisk-us.com/patients/products/product-patents.html\">http://novonordisk-us.com/patients/products/product-patents.html</a>\n</p>\n<p>© 2025 Novo Nordisk </p>\n<p>This Medication Guide has been approved by the U.S. Food and Drug Administration. </p>\n<p>Revised: 05/2025</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

INSTRUCTIONS FOR USE

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Victoza (liraglutide) injection

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First read the Medication Guide that comes with your Victoza single-patient use pen and then read this Patient Instructions for Use for information about how to use your Victoza pen the right way.

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These instructions do not take the place of talking with your healthcare provider about your medical condition or your treatment.

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Do not share your Victoza Pen with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them.

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Your Victoza pen is a disposable single-patient-use prefilled pen injector that contains 3 mL of Victoza and will deliver doses of 0.6 mg, 1.2 mg or 1.8 mg. The number of doses that you can take with a Victoza pen depends on the dose of medicine that is prescribed for you. Your healthcare provider will tell you how much Victoza to take.

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Victoza pen should be used with Novo Nordisk disposable needles. Talk to your healthcare provider or pharmacist for more information about needles for your Victoza pen.

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Important Information

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First Time Use for Each New Pen

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Step A. Check the Pen

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Step B. Attach the Needle

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Step C. Dial to the Flow Check Symbol

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This step is done only Once for each new pen and is Only required the first time you use a new pen.

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Step D. Prepare the Pen

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If you still see no drop of Victoza, use a new pen and contact Novo Nordisk at 1-877-484-2869.

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Continue to Step G under "Routine Use" →

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Routine Use

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Step E. Check the Pen

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Step F. Attach the Needle

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Step G. Dial the Dose

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Step H. Injecting the Dose

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Step I. Withdraw Needle

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Step J. Remove and Dispose of the Needle

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Caring for your Victoza pen

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How should I store Victoza?

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Before use:

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Pen in use:

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NDC 0169-4060-13

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List 406013

{ "type": "p", "children": [], "text": "List 406013" }

VICTOZA®

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(liraglutide) injection

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For Single Patient Use Only

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18 mg/3 mL (6 mg/mL)

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Each pen delivers doses of 0.6 mg, 1.2 mg or 1.8 mg

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Subcutaneous use only

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Discard pen 30 days after first use

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REFRIGERATE - DO NOT FREEZE

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Rx Only

{ "type": "p", "children": [], "text": "Rx Only" }

Contains: 3 Victoza Pens, Product Literature

{ "type": "p", "children": [], "text": "Contains: 3 Victoza Pens, Product Literature" }

Dispense the enclosed Medication Guide to each patient

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Intended for use with Novo Nordisk disposable needles

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3 Pens

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NDC 0169-4060-12

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List 406012

{ "type": "p", "children": [], "text": "List 406012" }

VICTOZA®

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(liraglutide) injection

{ "type": "p", "children": [], "text": "(liraglutide) injection" }

For Single Patient Use Only

{ "type": "p", "children": [], "text": "\nFor Single Patient Use Only\n" }

18 mg/3 mL (6 mg/mL)

{ "type": "p", "children": [], "text": "18 mg/3 mL (6 mg/mL)" }

Each pen delivers doses of 0.6 mg, 1.2 mg or 1.8 mg

{ "type": "p", "children": [], "text": "Each pen delivers doses of 0.6 mg, 1.2 mg or 1.8 mg" }

Subcutaneous use only

{ "type": "p", "children": [], "text": "Subcutaneous use only" }

Discard pen 30 days after first use

{ "type": "p", "children": [], "text": "Discard pen 30 days after first use" }

REFRIGERATE - DO NOT FREEZE

{ "type": "p", "children": [], "text": "\nREFRIGERATE - DO NOT FREEZE\n" }

Rx Only

{ "type": "p", "children": [], "text": "Rx Only" }

Contains: 2 Victoza Pens, Product Literature

{ "type": "p", "children": [], "text": "Contains: 2 Victoza Pens, Product Literature" }

Dispense the enclosed Medication Guide to each patient

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Intended for use with Novo Nordisk disposable needles

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2 Pens

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SAXENDA is indicated in combination with a reduced calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in:

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Limitations of Use

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Table 1. Dose Escalation Schedule

<div class="scrollingtable"><table width="100%"> <col width="26%"/> <col width="26%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Week</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Daily Dose</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.6 mg</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.2 mg</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.8 mg</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.4 mg</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5 and onward</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 mg</p> </td> </tr> </tbody> </table></div>

Pediatric Patients

Injection: 6 mg/mL clear, colorless solution in a 3 mL prefilled, single-patient-use pen that delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3 mg.

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SAXENDA is contraindicated in:

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Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors (adenomas and/or carcinomas) at clinically relevant exposures in both genders of rats and mice [see Nonclinical Toxicology (13.1)]. Malignant thyroid C-cell carcinomas were detected in rats and mice. It is unknown whether SAXENDA will cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.

Cases of MTC in patients treated with liraglutide have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and liraglutide use in humans.

SAXENDA is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of SAXENDA and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness).

Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with SAXENDA. Such monitoring may increase the risk of unnecessary procedures, due to low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin may indicate MTC, and patients with MTC usually have calcitonin values greater than 50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.

Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including liraglutide [see Adverse Reactions (6)]. After initiation of SAXENDA, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue SAXENDA and initiate appropriate management.

In SAXENDA clinical trials in adults, 2.2% of SAXENDA-treated patients reported adverse events of cholelithiasis versus 0.8% of placebo-treated patients. The incidence of cholecystitis was 0.8% in SAXENDA-treated patients versus 0.4% in placebo-treated patients. The majority of SAXENDA-treated patients with adverse events of cholelithiasis and cholecystitis required cholecystectomy. Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in SAXENDA-treated patients than in placebo-treated patients even after accounting for the degree of weight loss. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.

Adult patients with type 2 diabetes mellitus on an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia with use of SAXENDA, including severe hypoglycemia. In patients with type 2 diabetes, monitor blood glucose prior to starting SAXENDA and during SAXENDA treatment [see Dosage and Administration (2) and Adverse Reactions (6.1)].

The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.

In the pediatric clinical trial, patients did not have type 2 diabetes but were provided with blood glucose meters. Clinically significant hypoglycemia, defined as blood glucose <54 mg/dL, occurred in 1.6% of the SAXENDA- treated patients compared to 0.8% of placebo-treated patients [see Adverse Reactions (6.1)]. Inform all pediatric patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.

Mean increases in resting heart rate of 2 to 3 beats per minute (bpm) were observed with routine clinical monitoring in SAXENDA-treated adult patients compared to placebo in clinical trials. More patients treated with SAXENDA, compared with placebo, had changes from baseline at two consecutive visits of more than 10 bpm (34% versus 19%, respectively) and 20 bpm (5% versus 2%, respectively). At least one resting heart rate exceeding 100 bpm was recorded for 6% of SAXENDA-treated patients compared with 4% of placebo-treated patients, with this occurring at two consecutive study visits for 0.9% and 0.3%, respectively. Tachycardia was reported as an adverse reaction in 0.6% of SAXENDA-treated patients and in 0.1% of placebo-treated patients.

In a clinical pharmacology trial that monitored heart rate continuously for 24 hours, SAXENDA treatment was associated with a heart rate that was 4 to 9 bpm higher than that observed with placebo.

In a pediatric clinical trial, mean increases from baseline in resting heart rate of 3 to 7 bpm were observed with SAXENDA treatment.

Heart rate should be monitored at regular intervals consistent with usual clinical practice. Patients should inform health care providers of palpitations or feelings of a racing heartbeat while at rest during SAXENDA treatment. For patients who experience a sustained increase in resting heart rate while taking SAXENDA, SAXENDA should be discontinued.

There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with liraglutide [see Adverse Reactions (6.2)]. The majority of the reported events occurred in patients who had experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea [see Adverse Reactions (6.1)]. Monitor renal function in patients reporting adverse reactions to SAXENDA that could lead to volume depletion, especially during dosage initiation and escalation [see Use in Specific Populations (8.6)].

Use of GLP-1 receptor agonists, including liraglutide, has been associated with gastrointestinal adverse reactions, sometimes severe [see Adverse Reactions (6)]. In SAXENDA clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving SAXENDA (4.8%) than placebo

(1.4%). SAXENDA is not recommended in patients with severe gastroparesis.

There have been reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema) in patients treated with SAXENDA [see Contraindications (4), Adverse Reactions (6.1, 6.2)]. If a hypersensitivity reaction occurs, the patient should discontinue SAXENDA and other suspect medications and promptly seek medical advice.

Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists. Use caution in a patient with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to these reactions with SAXENDA.

In SAXENDA adult clinical trials, 9 (0.3%) of 3384 SAXENDA-treated patients and 2 (0.1%) of the 1941 placebo-treated patients reported suicidal ideation; one of these SAXENDA-treated patients attempted suicide.

In a SAXENDA pediatric clinical trial, 1 (0.8%) of the 125 SAXENDA-treated patients died by suicide. There was insufficient information to establish a causal relationship to SAXENDA.

Patients treated with SAXENDA should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue SAXENDA in patients who experience suicidal thoughts or behaviors. Avoid SAXENDA in patients with a history of suicidal attempts or active suicidal ideation.

SAXENDA delays gastric emptying [see Clinical Pharmacology (12.2)]. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations.

Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking SAXENDA, including whether modifying preoperative fasting recommendations or temporarily discontinuing SAXENDA could reduce the incidence of retained gastric contents. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking SAXENDA.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

SAXENDA was evaluated for safety in 5 double-blind, placebo controlled trials that included 3384 overweight or obese adult patients treated with SAXENDA for a treatment period up to 56 weeks (3 trials), 52 weeks (1 trial), and 32 weeks (1 trial) and one trial of 56 weeks in 125 pediatric patients with obesity aged 12 years and older [see Clinical Studies (14.1, 14.2)]. All patients received study drug in addition to a reduced-calorie diet and increased physical activity counseling. In the adult trials, patients received SAXENDA for a mean treatment duration of 46 weeks (median, 56 weeks). Baseline characteristics included a mean age of 47 years, 71% female, 85% white, 39% with hypertension, 15% with type 2 diabetes, 34% with dyslipidemia, 29% with a BMI greater than 40 kg/m2, and 9% with cardiovascular disease. In one of the 56-week trials, a subset of patients (with abnormal glucose measurements at randomization) [see Clinical Studies (14.1)] were enrolled for a placebo-controlled 160-week period instead, followed by a 12-week off-treatment follow-up. For those participating in this 160-week period, patients received SAXENDA for a mean treatment duration of 110 weeks (median, 159 weeks). For all trials, dosing was initiated and increased weekly to reach the 3 mg dose.

In adult clinical trials, 9.8% of patients treated with SAXENDA and 4.3% of patients treated with placebo prematurely discontinued treatment as a result of adverse reactions. The most common adverse reactions leading to discontinuation were nausea (2.9% versus 0.2% for SAXENDA and placebo, respectively), vomiting (1.7% versus less than 0.1%), and diarrhea (1.4% versus 0%).

Adverse reactions reported in greater than or equal to 2% of SAXENDA-treated adult patients and more frequently than in placebo-treated patients are shown in Table 2. Adverse reactions reported in greater than or equal to 3% of SAXENDA-treated pediatric patients and more frequently than in placebo-treated patients are shown in Table 3.

<div class="scrollingtable"><table width="457.35pt"> <col width="58%"/> <col width="20%"/> <col width="18%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">N = 1941</span> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">SAXENDA</span> </p> <p> <span class="Bold">N = 3384</span> </p> <p> <span class="Bold">%</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Nausea</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">13.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">39.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Diarrhea</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">9.9</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">20.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Constipation</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">19.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Vomiting</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.9</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">15.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Injection Site Reaction<span class="Sup">1</span> </dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">13.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Headache</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">12.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">13.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Hypoglycemia in T2DM<span class="Sup">2</span> </dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">12.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Dyspepsia</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">9.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Fatigue</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Dizziness</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Abdominal Pain</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Increased Lipase </dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Upper Abdominal Pain</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Gastroenteritis</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Gastroesophageal Reflux Disease</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Abdominal Distension</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Eructation</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Urinary Tract Infection</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Flatulence</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Viral Gastroenteritis </dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Insomnia</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Dry Mouth</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Asthenia</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.1</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>Anxiety</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2</p> </td> </tr> </tbody> </table></div>

1 The most common reactions, each reported by 1% to 2.5% of SAXENDA-treated patients and more commonly than by placebo-treated patients, included erythema, pruritus, and rash at the injection site.

2 Defined as blood glucose <54 mg/dL with or without symptoms of hypoglycemia in patients with type 2 diabetes not on concomitant insulin (Study 2, SAXENDA N=423, Placebo N=212). See text below for further information regarding hypoglycemia in patients with and without type 2 diabetes. T2DM = type 2 diabetes mellitus.

Table 3. Adverse Reactions Occurring in > 3% of SAXENDA-treated Pediatric Patients and More Frequently than Placebo in a 56 Week Clinical Trial

<div class="scrollingtable"><table width="82.52%"> <col width="58%"/> <col width="21%"/> <col width="17%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">N = 126</span> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">SAXENDA</span> </p> <p> <span class="Bold">N = 125</span> </p> <p> <span class="Bold">%</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Nausea</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">14.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">42.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Vomiting</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">34.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Diarrhea</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">14.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">22.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Hypoglycemia<span class="Sup">1</span> </dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">15.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Gastroenteritis</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">12.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Dizziness</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Pyrexia</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Abdominal discomfort</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Constipation</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Dyslipidemia</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Fatigue</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Cough</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Depression</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Dyspepsia</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Pain in extremity</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Injection site pain</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Flatulence</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Increased Blood Creatine Kinase</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Increased Lipase </dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.2</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt> </dt> <dd>Rash</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.2</p> </td> </tr> </tbody> </table></div>

1 Defined as blood glucose <70 mg/dL with symptoms of hypoglycemia. Pediatric patients did not have type 2 diabetes mellitus. See text below for more detailed hypoglycemia information.

Hypoglycemia

Adult Patients with Type 2 Diabetes

In a clinical trial in adult patients with type 2 diabetes mellitus and overweight (excess weight) or obesity, severe hypoglycemia (defined as requiring the assistance of another person) occurred in 3 (0.7%) of 422 SAXENDA-treated patients (all taking a sulfonylurea) and in none of the 212 placebo-treated patients. In this trial, among patients taking a sulfonylurea, hypoglycemia defined as a plasma glucose less than 54 mg/dL with or without symptoms occurred in 31 (28.2%) of 110 SAXENDA-treated patients and 7 (12.7%) of 55 placebo-treated patients. The doses of sulfonylureas were reduced by 50% at the beginning of the trial per protocol. Among patients not taking a sulfonylurea, blood glucose less than 54 mg/dL with or without symptoms occurred in 22 (7.1%) of 312 SAXENDA-treated patients and 7 (4.5%) of 157 placebo-treated patients.

In a SAXENDA clinical trial in adult patients with overweight (excess weight) or obesity with type 2 diabetes mellitus treated with basal insulin and SAXENDA in combination with a reduced-calorie diet and increased physical activity and up to 2 oral anti-diabetes medications, severe hypoglycemia was reported by 3 (1.5%) of 195 SAXENDA-treated patients and 2 (1%) of 197 placebo-treated patients. No meaningful difference in hypoglycemia, defined as blood glucose less than 54 mg/dL with or without symptoms, was reported between groups.

Adult Patients without Type 2 Diabetes

In SAXENDA clinical trials in adult patients without type 2 diabetes mellitus, there was no systematic capturing or reporting of hypoglycemia; patients were not provided with blood glucose meters or hypoglycemia diaries. Spontaneously reported symptomatic episodes of unconfirmed hypoglycemia were reported by 46 (1.6%) of 2962 SAXENDA-treated patients and 19 (1.1%) of 1729 placebo-treated patients. Fasting plasma glucose values obtained at routine clinic visits less than 54 mg/dL, irrespective of hypoglycemic symptoms, occurred in 2 (0.1%) SAXENDA-treated patients and 1 (0.1%) placebo-treated patients.

Pediatric Patients without Type 2 Diabetes

In a 56-week placebo-controlled clinical trial of pediatric patients without type 2 diabetes mellitus in which blood glucose meters were provided, 19 (15.2%) of SAXENDA-treated patients had hypoglycemia with a blood glucose less than 70 mg/dL with symptoms as compared to 5 (4%) of placebo-treated patients. Four (4) events of hypoglycemia defined as a plasma glucose less than 54 mg/dL occurred in 2 (1.6%) of 125 SAXENDA-treated patients and 1 event occurred in 1 (0.8%) of 126 placebo-treated patients. No severe hypoglycemic episodes, defined as requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, occurred in the SAXENDA treatment group.

Acute Pancreatitis

In SAXENDA clinical trials in adults, acute pancreatitis was confirmed by adjudication in 9 (0.3%) of 3291 SAXENDA-treated patients and 2 (0.1%) of 1843 placebo-treated patients. In addition, there were 2 cases of acute pancreatitis in SAXENDA-treated patients who prematurely withdrew from these clinical trials, occurring 74 and 124 days after the last dose. There were 2 additional cases in SAXENDA-treated patients, 1 during an off-treatment follow-up period within 2 weeks of discontinuing SAXENDA, and 1 that occurred in a patient who completed treatment and was off-treatment for 106 days.

In a SAXENDA pediatric clinical trial, pancreatitis was not independently adjudicated. Pancreatitis was reported in 1 (0.8%) SAXENDA-treated patient and resulted in treatment discontinuation.

Gastrointestinal Adverse Reactions

In the adult clinical trials, approximately 68% of SAXENDA-treated patients and 39% of placebo-treated patients reported gastrointestinal disorders; the most frequently reported was nausea (39% and 14% of patients treated with SAXENDA and placebo, respectively). Severe gastrointestinal adverse reactions were reported more frequently among patients receiving SAXENDA (4.8%) than placebo (1.4 %). There have been reports of gastrointestinal adverse reactions, such as nausea, vomiting, and diarrhea, associated with volume depletion and renal impairment. Most episodes of gastrointestinal events were mild or moderate and did not lead to discontinuation of therapy (6.2% with SAXENDA versus 0.8% with placebo discontinued treatment as a result of gastrointestinal adverse reactions). The percentage of patients reporting nausea declined as treatment continued. Other common adverse reactions that occurred at a higher incidence among SAXENDA-treated patients included diarrhea, constipation, vomiting, dyspepsia, abdominal pain, dry mouth, gastritis, gastroesophageal reflux disease, flatulence, eructation and abdominal distension. There have been reports of gastrointestinal adverse reactions, such as nausea, vomiting, and diarrhea, associated with volume depletion and renal impairment.

In a pediatric clinical trial, 8% of patients treated with SAXENDA versus no patients who received placebo discontinued treatment as a result of gastrointestinal adverse reactions. Most adverse reactions leading to discontinuation were due to vomiting and nausea (4.8% and 3.2% of SAXENDA-treated patients, respectively).

Asthenia, Fatigue, Malaise, Dysgeusia and Dizziness

Events of asthenia, fatigue, malaise, dysgeusia and dizziness were mainly reported within the first 12 weeks of treatment with SAXENDA and were often co-reported with gastrointestinal events such as nausea, vomiting, and diarrhea.

Immunogenicity

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, the incidence of antibodies to SAXENDA cannot be directly compared with the incidence of antibodies of other products.

Patients treated with SAXENDA may develop anti-liraglutide antibodies. Anti-liraglutide antibodies were detected in 42 (2.8%) of 1505 SAXENDA-treated adult patients with a post-baseline assessment. Antibodies that had a neutralizing effect on liraglutide in an in vitro assay occurred in 18 (1.2%) of 1505 SAXENDA-treated patients. Presence of antibodies may be associated with a higher incidence of injection site reactions and reports of low blood glucose. In clinical trials, these events were usually classified as mild and resolved while patients continued on treatment.

In a pediatric clinical trial, anti-liraglutide antibodies were detected in 14 (12%) of 117 SAXENDA-treated patients with a post-baseline assessment; 5 (4.3%) had persistent antibodies as defined by more than 2 antibody visits at least 16 weeks apart. Two patients (1.7%) remained positive throughout the follow-up period; 1 (0.9%) had antibodies cross reactive to native GLP-1. No patients had neutralizing antibodies.

Allergic Reactions

Urticaria was reported in 0.7% of SAXENDA-treated patients and 0.5% of placebo-treated patients. Anaphylactic reactions, asthma, bronchial hyperreactivity, bronchospasm, oropharyngeal swelling, facial swelling, angioedema, pharyngeal edema, type IV hypersensitivity reactions have been reported in patients treated with liraglutide in clinical trials. Cases of anaphylactic reactions with additional symptoms such as hypotension, palpitations, dyspnea, and edema have been reported with marketed use of liraglutide. Anaphylactic reactions may potentially be life-threatening.

Breast Cancer

In SAXENDA clinical trials in adults, breast cancer confirmed by adjudication was reported in 17 (0.7%) of 2379 SAXENDA-treated women compared with 3 (0.2%) of 1300 placebo-treated women, including invasive cancer (13 SAXENDA- and 2 placebo-treated women) and ductal carcinoma in situ (4 SAXENDA- and 1 placebo-treated woman). The majority of cancers were estrogen- and progesterone-receptor positive. There were too few cases to determine whether these cases were related to SAXENDA. In addition, there are insufficient data to determine whether SAXENDA has an effect on pre-existing breast neoplasia.

Papillary Thyroid Cancer

In SAXENDA clinical trials in adults, papillary thyroid carcinoma confirmed by adjudication was reported in 8 (0.2%) of 3291 SAXENDA-treated patients compared with no cases among 1843 placebo-treated patients. Four of these papillary thyroid carcinomas were less than 1 cm in greatest diameter and 4 were diagnosed in surgical pathology specimens after thyroidectomy prompted by findings identified prior to treatment.

Colorectal Neoplasms

In SAXENDA clinical trials in adults, benign colorectal neoplasms (mostly colon adenomas) confirmed by adjudication were reported in 20 (0.6%) of 3291 SAXENDA-treated patients compared with 7 (0.4%) of 1843 placebo-treated patients. Six positively adjudicated cases of malignant colorectal neoplasms were reported in 5 SAXENDA-treated patients (0.2%, mostly adenocarcinomas) and 1 in a placebo-treated patient (0.1%, neuroendocrine tumor of the rectum).

Cardiac Conduction Disorders

In SAXENDA clinical trials in adults, 11 (0.3%) of 3384 SAXENDA-treated patients compared with none of the 1941 placebo-treated patients had a cardiac conduction disorder, reported as first degree atrioventricular block, right bundle branch block, or left bundle branch block.

Hypotension

Adverse reactions related to hypotension (hypotension, orthostatic hypotension, circulatory collapse, and decreased blood pressure) were reported more frequently with SAXENDA (1.1%) compared with placebo (0.5%) in SAXENDA clinical trials in adults. Systolic blood pressure decreases to less than 80 mmHg were observed in 4 (0.1%) SAXENDA-treated patients compared with no placebo-treated patients. One of the SAXENDA-treated patients had hypotension associated with gastrointestinal adverse reactions and renal failure [see Warnings and Precautions (5.6)].

Laboratory Abnormalities

Liver Enzymes

Increases in alanine aminotransferase (ALT) greater than or equal to 10 times the upper limit of normal were observed in 5 (0.15%) SAXENDA-treated patients (two of whom had ALT greater than 20 and 40 times the upper limit of normal) compared with 1 (0.05%) placebo-treated patient during the SAXENDA clinical trials. Because clinical evaluation to exclude alternative causes of ALT and aspartate aminotransferase (AST) increases was not done in most cases, the relationship to SAXENDA is uncertain. Some increases in ALT and AST were associated with other confounding factors (such as gallstones).

Serum Calcitonin

Calcitonin, a biological marker of MTC, was measured throughout the clinical development program [see Warnings and Precautions (5.1)]. More patients treated with SAXENDA in the clinical trials were observed to have high calcitonin values during treatment, compared with placebo. The proportion of patients with calcitonin greater than or equal to 2 times the upper limit of normal at the end of the trial was 1.2% in SAXENDA-treated patients and 0.6% in placebo-treated patients. Calcitonin values greater than 20 ng/L at the end of the trial occurred in 0.5% of SAXENDA-treated patients and 0.2% of placebo-treated patients; among patients with pre-treatment serum calcitonin less than 20 ng/L, none had calcitonin elevations to greater than 50 ng/L at the end of the trial.

Serum Lipase and Amylase

Serum lipase and amylase were routinely measured in the SAXENDA clinical trials. Among SAXENDA-treated patients, 2.1% had a lipase value at anytime during treatment of greater than or equal to 3 times the upper limit of normal compared with 1.0% of placebo-treated patients. 0.1% of SAXENDA-treated patients had an amylase value at anytime in the trial of greater than or equal to 3 times the upper limit of normal versus 0.1% of placebo-treated patients. The clinical significance of elevations in lipase or amylase with SAXENDA is unknown in the absence of other signs and symptoms of pancreatitis [see Warnings and Precautions (5.2)].

The following adverse reactions have been reported during post-approval use of liraglutide, the active ingredient of SAXENDA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal

Hepatobiliary

Hypersensitivity

Neoplasms

Neurologic

Pulmonary

Renal

Acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis; increased serum creatinine

General Disorders and Administration Site Conditions

Allergic reactions: rash and pruritus

Immune System

Skin and Subcutaneous Tissue

SAXENDA causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, liraglutide did not affect the absorption of the tested orally administered medications to any clinically relevant degree. Nonetheless, monitor for potential consequences of delayed absorption of oral medications concomitantly administered with SAXENDA.

Risk Summary

Based on animal reproduction studies, there may be risks to the fetus from exposure to SAXENDA during pregnancy. SAXENDA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Additionally, weight loss offers no benefit to a pregnant patient and may cause fetal harm. When a pregnancy is recognized, advise the pregnant patient of the risk to a fetus, and discontinue SAXENDA (see Clinical Considerations).

Animal reproduction studies identified increased adverse embryofetal developmental outcomes from exposure during pregnancy. Liraglutide exposure was associated with early embryonic deaths and an imbalance in some fetal abnormalities in pregnant rats administered liraglutide during organogenesis at doses that approximate clinical exposures at the maximum recommended human dose (MRHD) of 3 mg/day. In pregnant rabbits administered liraglutide during organogenesis, decreased fetal weight and an increased incidence of major fetal abnormalities were seen at exposures below the human exposures at the MRHD (see Animal Data).

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage of clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryofetal risk

Appropriate weight gain based on pre-pregnancy weight is currently recommended for all pregnant patients, including those who already have overweight or obesity, because of the obligatory weight gain that occurs in maternal tissues during pregnancy.

Animal Data

Liraglutide has been shown to be teratogenic in rats at or above 0.8-times systemic exposures in obese humans resulting from the maximum recommended human dose (MRHD) of 3 mg/day based on plasma area under the time-concentration curve (AUC) comparison. Liraglutide has been shown to cause reduced growth and increased total major abnormalities in rabbits at systemic exposures below exposure in obese humans at the MRHD based on plasma AUC comparison.

Female rats given subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide beginning 2 weeks before mating through gestation day 17 had estimated systemic exposures 0.8-, 3-, and 11-times the exposure in obese humans at the MRHD based on plasma AUC comparison. The number of early embryonic deaths in the 1 mg/kg/day group increased slightly. Fetal abnormalities and variations in kidneys and blood vessels, irregular ossification of the skull, and a more complete state of ossification occurred at all doses. Mottled liver and minimally kinked ribs occurred at the highest dose. The incidence of fetal malformations in liraglutide-treated groups exceeding concurrent and historical controls were misshapen oropharynx and/or narrowed opening into larynx at 0.1 mg/kg/day and umbilical hernia at 0.1 and 0.25 mg/kg/day.

Pregnant rabbits given subcutaneous doses of 0.01, 0.025 and 0.05 mg/kg/day liraglutide from gestation day 6 through day 18 inclusive, had estimated systemic exposures less than the exposure in obese humans at the MRHD of 3 mg/day at all doses, based on plasma AUC comparison. Liraglutide decreased fetal weight and dose-dependently increased the incidence of total major fetal abnormalities at all doses. The incidence of malformations exceeded concurrent and historical controls at 0.01 mg/kg/day (kidneys, scapula), greater than or equal to 0.01 mg/kg/day (eyes, forelimb), 0.025 mg/kg/day (brain, tail and sacral vertebrae, major blood vessels and heart, umbilicus), greater than or equal to 0.025 mg/kg/day (sternum) and at 0.05 mg/kg/day (parietal bones, major blood vessels). Irregular ossification and/or skeletal abnormalities occurred in the skull and jaw, vertebrae and ribs, sternum, pelvis, tail, and scapula; and dose-dependent minor skeletal variations were observed. Visceral abnormalities occurred in blood vessels, lung, liver, and esophagus. Bilobed or bifurcated gallbladder was seen in all treatment groups, but not in the control group.

In pregnant female rats given subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide from gestation day 6 through weaning or termination of nursing on lactation day 24, estimated systemic exposures were 0.8-, 3-, and 11-times exposure in obese humans at the MRHD of 3 mg/day, based on plasma AUC comparison. A slight delay in parturition was observed in the majority of treated rats. Group mean body weight of neonatal rats from liraglutide-treated dams was lower than neonatal rats from control group dams. Bloody scabs and agitated behavior occurred in male rats descended from dams treated with 1 mg/kg/day liraglutide. Group mean body weight from birth to postpartum day 14 trended lower in F2 generation rats descended from liraglutide-treated rats compared to F2 generation rats descended from controls, but differences did not reach statistical significance for any group.

Risk Summary

There are no data on the presence of liraglutide in human milk, the effects on the breastfed infant, or effects on milk production. Liraglutide was present in the milk of lactating rats (see Data).

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SAXENDA and any potential adverse effects on the breastfed infant from SAXENDA or from the underlying maternal condition.

Data

In lactating rats, liraglutide was present unchanged in milk at concentrations approximately 50% of maternal plasma concentrations.

The safety and effectiveness of SAXENDA as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management have been established in pediatric patients aged 12 years and older with body weight above 60 kg and an initial BMI corresponding to 30 kg/m2 or greater for adults (obese) by international cut-offs. Use of SAXENDA for this indication is supported by a 56-week double-blind, placebo-controlled clinical trial in 251 pediatric patients aged 12 to 17 years, a pharmacokinetic study in pediatric patients, and studies in adults with obesity [see Clinical Pharmacology (12.3), Clinical Studies (14.1, 14.2)].

In the pediatric clinical trial, there was one death due to suicide in a SAXENDA-treated patient [see Warnings and Precautions (5.8)]; one SAXENDA-treated patient had an event of pancreatitis [see Warnings and Precautions (5.2)]; more episodes of hypoglycemia confirmed by self blood glucose monitoring occurred in SAXENDA-treated patients compared to placebo [see Warnings and Precautions (5.4), Adverse Reactions (6.1)]; and mean increases in resting heart rate of 3 to 7 bpm from baseline were observed with SAXENDA-treated patients [see Warnings and Precautions (5.5)].

The safety and effectiveness of SAXENDA have not been established in patients less than 12 years of age.

In the SAXENDA clinical trials, 232 (6.9%) of the SAXENDA-treated patients were 65 years of age and over, and 17 (0.5%) of the SAXENDA-treated patients were 75 years of age and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

There is limited experience with SAXENDA in patients with mild, moderate, and severe renal impairment, including end‑stage renal disease.

There is limited experience in patients with mild, moderate, or severe hepatic impairment. Therefore, SAXENDA should be used with caution in this patient population [see Clinical Pharmacology (12.3)].

Overdoses have been reported in clinical trials and post-marketing use of liraglutide. Effects have included severe nausea, severe vomiting and severe hypoglycemia. In the event of overdosage, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Initiate appropriate supportive treatment according to the patient’s clinical signs and symptoms.

{ "type": "p", "children": [], "text": "Overdoses have been reported in clinical trials and post-marketing use of liraglutide. Effects have included severe nausea, severe vomiting and severe hypoglycemia. In the event of overdosage, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Initiate appropriate supportive treatment according to the patient’s clinical signs and symptoms." }

SAXENDA contains liraglutide, an analog of human GLP-1 and acts as a GLP-1 receptor agonist. The peptide precursor of liraglutide, produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae, has been engineered to be 97% homologous to native human GLP-1 by substituting arginine for lysine at position 34. Liraglutide is made by attaching a C-16 fatty acid (palmitic acid) with a glutamic acid spacer on the remaining lysine residue at position 26 of the peptide precursor. The molecular formula of liraglutide is C172H265N43O51 and the molecular weight is 3751.2 Daltons. The structural formula (Figure 1) is:

{ "type": "p", "children": [], "text": "SAXENDA contains liraglutide, an analog of human GLP-1 and acts as a GLP-1 receptor agonist. The peptide precursor of liraglutide, produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae, has been engineered to be 97% homologous to native human GLP-1 by substituting arginine for lysine at position 34. Liraglutide is made by attaching a C-16 fatty acid (palmitic acid) with a glutamic acid spacer on the remaining lysine residue at position 26 of the peptide precursor. The molecular formula of liraglutide is C172H265N43O51 and the molecular weight is 3751.2 Daltons. The structural formula (Figure 1) is:" }

Figure 1. Structural Formula of liraglutide

{ "type": "p", "children": [], "text": "\nFigure 1. Structural Formula of liraglutide\n" }

SAXENDA injection is a sterile, aqueous, clear, colorless or almost colorless solution for subcutaneous use. Each 1 mL of SAXENDA solution contains 6 mg of liraglutide and the following inactive ingredients: disodium phosphate dihydrate, 1.42 mg; propylene glycol, 14 mg; phenol, 5.5 mg; and water for injection. SAXENDA has a pH of approximately 8.15, hydrochloric acid or sodium hydroxide may be added to adjust pH. Each prefilled pen contains a 3 mL solution of SAXENDA equivalent to 18 mg liraglutide (free-base, anhydrous).

{ "type": "p", "children": [], "text": "SAXENDA injection is a sterile, aqueous, clear, colorless or almost colorless solution for subcutaneous use. Each 1 mL of SAXENDA solution contains 6 mg of liraglutide and the following inactive ingredients: disodium phosphate dihydrate, 1.42 mg; propylene glycol, 14 mg; phenol, 5.5 mg; and water for injection. SAXENDA has a pH of approximately 8.15, hydrochloric acid or sodium hydroxide may be added to adjust pH. Each prefilled pen contains a 3 mL solution of SAXENDA equivalent to 18 mg liraglutide (free-base, anhydrous)." }

Liraglutide is an acylated human GLP-1 receptor agonist with 97% amino acid sequence homology to endogenous human GLP-1(7-37). Like endogenous GLP-1, liraglutide binds to and activates the GLP-1 receptor, a cell-surface receptor coupled to adenylyl cyclase activation through the stimulatory G-protein, Gs. Endogenous GLP-1 has a half-life of 1.5 to 2 minutes due to degradation by the ubiquitous endogenous enzymes, dipeptidyl peptidase 4 (DPP-4) and neutral endopeptidases (NEP). Unlike native GLP-1, liraglutide is stable against metabolic degradation by both peptidases and has a plasma half-life of 13 hours after subcutaneous administration. The pharmacokinetic profile of liraglutide, which makes it suitable for once-daily administration, is a result of self-association that delays absorption, plasma protein binding, and stability against metabolic degradation by DPP-4 and NEP.

GLP-1 is a physiological regulator of appetite and calorie intake, and the GLP-1 receptor is present in several areas of the brain involved in appetite regulation. In animal studies, peripheral administration of liraglutide resulted in the presence of liraglutide in specific brain regions regulating appetite, including the hypothalamus. Although liraglutide activated neurons in brain regions known to regulate appetite, specific brain regions mediating the effects of liraglutide on appetite were not identified in rats.

Liraglutide lowers body weight through decreased calorie intake. Liraglutide does not increase 24-hour energy expenditure.

As with other GLP-1 receptor agonists, liraglutide stimulates insulin secretion and reduces glucagon secretion in a glucose-dependent manner. These effects can lead to a reduction of blood glucose.

Gastric Emptying

Liraglutide delays gastric emptying.

Cardiac Electrophysiology (QTc) in healthy volunteers

The effect of liraglutide on cardiac repolarization was tested in a QTc study. Liraglutide at steady-state concentrations after daily doses up to 1.8 mg did not produce QTc prolongation. The maximum liraglutide plasma concentration (Cmax) in overweight and obese subjects treated with liraglutide 3 mg is similar to the Cmax observed in the liraglutide QTc study in healthy volunteers.

Absorption - Following subcutaneous administration, maximum concentrations of liraglutide are achieved at 11 hours post dosing. The average liraglutide steady state concentration (AUCτ/24) reached approximately 116 ng/mL in obese (BMI 30-40 kg/m2) subjects following administration of SAXENDA. Liraglutide exposure increased proportionally in the dose range of 0.6 mg to 3 mg. The intra-subject coefficient of variation for liraglutide AUC was 11% following single dose administration. Liraglutide exposures were considered similar among three subcutaneous injection sites (upper arm, abdomen, and thigh). Absolute bioavailability of liraglutide following subcutaneous administration is approximately 55%.

Distribution - The mean apparent volume of distribution after subcutaneous administration of liraglutide 3 mg is 20 to 25L (for a person weighing approximately 100 kg). The mean volume of distribution after intravenous administration of liraglutide is 0.07 L/kg. Liraglutide is extensively bound to plasma protein (greater than 98%).

Metabolism - During the initial 24 hours following administration of a single [3H]-liraglutide dose to healthy subjects, the major component in plasma was intact liraglutide. Liraglutide is endogenously metabolized in a similar manner to large proteins without a specific organ as a major route of elimination.

Elimination - Following a [3H]-liraglutide dose, intact liraglutide was not detected in urine or feces. Only a minor part of the administered radioactivity was excreted as liraglutide-related metabolites in urine or feces (6% and 5%, respectively). The majority of urine and feces radioactivity was excreted during the first 6 to 8 days. The mean apparent clearance following subcutaneous administration of a single dose of liraglutide is approximately 0.9 to 1.4 L/h with an elimination half-life of approximately 13 hours, making liraglutide suitable for once daily administration.

Specific Populations

Elderly - Age had no effect on the pharmacokinetics of liraglutide based on a pharmacokinetic study in healthy elderly subjects (65 to 83 years) and population pharmacokinetic analyses of data from overweight and obese patients 18 to 82 years of age [see Use in Specific Populations (8.5)].

Gender - Based on the results of population pharmacokinetic analyses, females have 24% lower weight adjusted clearance of SAXENDA compared to males.

Race and Ethnicity - Race and ethnicity had no effect on the pharmacokinetics of liraglutide based on the results of population pharmacokinetic analyses that included overweight and obese patients of White, Black or African American, Asian and Hispanic/Non-Hispanic Ethnic groups.

Body Weight - Body weight significantly affects the pharmacokinetics of liraglutide based on results of population pharmacokinetic analyses conducted in patients with body weight range of 60 to 234 kg. The exposure of liraglutide decreases as baseline body weight increases.

Pediatric - A population pharmacokinetic analysis was conducted for SAXENDA using data from 134 pediatric patients (12 to 17 years of age) with obesity. The liraglutide exposure in the pediatric patients was similar to that in adults with obesity [see Use in Specific Populations (8.4)].

Renal Impairment - The single-dose pharmacokinetics of liraglutide were evaluated in patients with varying degrees of renal impairment. Patients with mild (estimated creatinine clearance 50-80 mL/min) to severe (estimated creatinine clearance less than 30 mL/min) renal impairment and patients with end-stage renal disease requiring dialysis were included in the trial. Compared to healthy subjects, liraglutide AUC in mild, moderate, and severe renal impairment and in end-stage renal disease was on average 35%, 19%, 29% and 30% lower, respectively [see Use in Specific Populations (8.6)].

Hepatic Impairment - The single-dose pharmacokinetics of liraglutide were evaluated in patients with varying degrees of hepatic impairment. Patients with mild (Child Pugh score 5 to 6) to severe (Child Pugh score greater than 9) hepatic impairment were included in the trial. Compared to healthy subjects, liraglutide AUC in subjects with mild, moderate and severe hepatic impairment was on average 11%, 14% and 42% lower, respectively [see Use in Specific Populations (8.7)].

Drug Interactions

In vitro assessment of drug−drug interactions

Liraglutide has low potential for pharmacokinetic drug-drug interactions related to cytochrome P450 (CYP) and plasma protein binding.

In vivo assessment of drug−drug interactions

The drug-drug interaction studies were performed at steady state with liraglutide 1.8 mg/day. The effect on rate of gastric emptying was equivalent between liraglutide 1.8 mg and 3 mg (acetaminophen AUC0-300min).

Administration of the interacting drugs was timed so that Cmax of liraglutide (8-12 h) would coincide with the absorption peak of the co-administered drugs.

Oral Contraceptives

A single dose of an oral contraceptive combination product containing 0.03 mg ethinylestradiol and 0.15 mg levonorgestrel was administered under fed conditions and 7 hours after the dose of liraglutide at steady state. Liraglutide lowered ethinylestradiol and levonorgestrel Cmax by 12% and 13%, respectively. There was no effect of liraglutide on the overall exposure (AUC) of ethinylestradiol. Liraglutide increased the levonorgestrel AUC0-∞ by 18%. Liraglutide delayed Tmax for both ethinylestradiol and levonorgestrel by 1.5 h.

Digoxin

A single dose of digoxin 1 mg was administered 7 hours after the dose of liraglutide at steady state. The concomitant administration with liraglutide resulted in a reduction of digoxin AUC by 16%; Cmax decreased by 31%. Digoxin median time to maximal concentration (Tmax) was delayed from 1 h to 1.5 h.

Lisinopril

A single dose of lisinopril 20 mg was administered 5 minutes after the dose of liraglutide at steady state. The coadministration with liraglutide resulted in a reduction of lisinopril AUC by 15%; Cmax decreased by 27%. Lisinopril median Tmax was delayed from 6 h to 8 h with liraglutide.

Atorvastatin

Liraglutide did not change the overall exposure (AUC) of atorvastatin following a single dose of atorvastatin 40 mg, administered 5 hours after the dose of liraglutide at steady state. Atorvastatin Cmax was decreased by 38% and median Tmax was delayed from 1 h to 3 h with liraglutide.

Acetaminophen

Liraglutide did not change the overall exposure (AUC) of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after the dose of liraglutide at steady state. Acetaminophen Cmax was decreased by 31% and median Tmax was delayed up to 15 minutes.

Griseofulvin

Liraglutide did not change the overall exposure (AUC) of griseofulvin following co-administration of a single dose of griseofulvin 500 mg with liraglutide at steady state. Griseofulvin Cmax increased by 37% while median Tmax did not change.

Insulin Detemir

No pharmacokinetic interaction was observed between liraglutide and insulin detemir when separate subcutaneous injections of insulin detemir 0.5 Unit/kg (single-dose) and liraglutide 1.8 mg (steady state) were administered to patients with type 2 diabetes mellitus.

A 104-week carcinogenicity study was conducted in male and female CD-1 mice at doses of 0.03, 0.2, 1, and 3 mg/kg/day liraglutide administered by bolus subcutaneous injection yielding systemic exposures 0.2-, 2-, 10- and 43-times the exposure in obese humans, respectively, at the maximum recommended human dose (MRHD) of 3 mg/day based on plasma AUC comparison. A dose-related increase in benign thyroid C-cell adenomas was seen in the 1 and the 3 mg/kg/day groups with incidences of 13% and 19% in males and 6% and 20% in females, respectively. C-cell adenomas did not occur in control groups or 0.03 and 0.2 mg/kg/day groups. Treatment-related malignant C-cell carcinomas occurred in 3% of females in the 3 mg/kg/day group. Thyroid C-cell tumors are rare findings during carcinogenicity testing in mice. A treatment-related increase in fibrosarcomas was seen on the dorsal skin and subcutis, the body surface used for drug injection, in males in the 3 mg/kg/day group. These fibrosarcomas were attributed to the high local concentration of drug near the injection site. The liraglutide concentration in the clinical formulation (6 mg/mL) is 10-times higher than the concentration in the formulation used to administer 3 mg/kg/day liraglutide to mice in the carcinogenicity study (0.6 mg/mL).

A 104-week carcinogenicity study was conducted in male and female Sprague Dawley rats at doses of 0.075, 0.25 and 0.75 mg/kg/day liraglutide administered by bolus subcutaneous injection with exposures 0.5-, 2- and 7-times the exposure in obese humans, respectively, resulting from the MRHD based on plasma AUC comparison. A treatment-related increase in benign thyroid C-cell adenomas was seen in males in 0.25 and 0.75 mg/kg/day liraglutide groups with incidences of 12%, 16%, 42%, and 46% and in all female liraglutide-treated groups with incidences of 10%, 27%, 33%, and 56% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups, respectively. A treatment-related increase in malignant thyroid C-cell carcinomas was observed in all male liraglutide-treated groups with incidences of 2%, 8%, 6%, and 14% and in females at 0.25 and 0.75 mg/kg/day with incidences of 0%, 0%, 4%, and 6% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups, respectively. Thyroid C-cell carcinomas are rare findings during carcinogenicity testing in rats.

Studies in mice demonstrated that liraglutide-induced C-cell proliferation was dependent on the GLP-1 receptor and that liraglutide did not cause activation of the REarranged during Transfection (RET) proto-oncogene in thyroid C-cells.

Human relevance of thyroid C-cell tumors in mice and rats is unknown and has not been determined by clinical studies or nonclinical studies [see Boxed Warning, Warnings and Precautions (5.1)].

Liraglutide was negative with and without metabolic activation in the Ames test for mutagenicity and in a human peripheral blood lymphocyte chromosome aberration test for clastogenicity. Liraglutide was negative in repeat-dose in vivo micronucleus tests in rats.

In rat fertility studies using subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide, males were treated for 4 weeks prior to and throughout mating and females were treated 2 weeks prior to and throughout mating until gestation day 17. No direct adverse effects on male fertility was observed at doses up to 1 mg/kg/day, a high dose yielding an estimated systemic exposure 11-times the exposure in obese humans at the MRHD, based on plasma AUC comparison. In female rats, an increase in early embryonic deaths occurred at 1 mg/kg/day. Reduced body weight gain and food consumption were observed in females at the 1 mg/kg/day dose.

The safety and efficacy of SAXENDA for chronic weight management in conjunction with reduced caloric intake and increased physical activity were studied in three 56-week, randomized, double-blind, placebo-controlled trials. In all studies, SAXENDA was titrated to 3 mg daily during a 4-week period. All patients received instruction for a reduced-calorie diet (approximately 500 kcal/day deficit) and physical activity counseling (recommended increase in physical activity of minimum 150 mins/week) that began with the first dose of study medication or placebo and continued throughout the trial.

Study 1 enrolled 3731 patients with obesity (BMI greater than or equal to 30 kg/m2) or with overweight (BMI 27-29.9 kg/m2) and at least one weight-related comorbid condition such as treated or untreated dyslipidemia or hypertension; patients with type 2 diabetes mellitus were excluded. Patients were randomized in a 2:1 ratio to either SAXENDA or placebo. Patients were stratified based on the presence or absence of abnormal blood glucose measurements at randomization. All patients were treated for up to 56 weeks. Those patients with abnormal glucose measurements at randomization (2254 of the 3731 patients) were treated for a total of 160 weeks. At baseline, mean age was 45 years (range 18 to 78), 79% were female, 85% were White, 10% were Black or African American, and 11% were Hispanic/Latino Ethnicity. Mean baseline body weight was 106.3 kg and mean BMI was 38.3 kg/m2.

Study 2 was a 56-week trial that enrolled 635 patients with type 2 diabetes and with either overweight or obesity (as defined above). Patients were to have an HbA1c of 7% to 10% and be treated with metformin, a sulfonylurea, or a glitazone as single agent or in any combination, or with a reduced-calorie diet and physical activity alone. Patients were randomized in a 2:1 ratio to receive either SAXENDA or placebo. The mean age was 55 years (range 18 to 82), 50% were female, 83% were White, 12% were Black or African American, and 10% were Hispanic/Latino Ethnicity. Mean baseline body weight was 105.9 kg and mean BMI was 37.1 kg/m2.

Study 3 was a 56-week trial that enrolled 422 patients with obesity (BMI greater than or equal to 30 kg/m2) or with overweight (BMI 27-29.9 kg/m2) and at least one weight-related comorbid condition such as treated or untreated dyslipidemia or hypertension; patients with type 2 diabetes mellitus were excluded. All patients were first treated with a low-calorie diet (total energy intake 1200-1400 kcal/day) in a run-in period lasting up to 12 weeks. Patients who lost at least 5% of their screening body weight after 4 to 12 weeks during the run-in were then randomized, with equal allocation, to receive either SAXENDA or placebo for 56 weeks. The mean age was 46 years (range 18 to 73), 81% were female, 84% were White, 13% were Black or African American, and 7% were Hispanic/Latino Ethnicity. Mean baseline body weight was 99.6 kg and mean BMI was 35.6 kg/m2.

The proportions of patients who discontinued study drug in the 56-week trials were 27% for the SAXENDA-treated group and 35% for the placebo-treated group, and in the 160-week trial the proportions of patients who discontinued were 47% and 55%, respectively. In the 56-week trials, approximately 10% of patients treated with SAXENDA and 4% of patients treated with placebo discontinued treatment due to an adverse reaction [see Adverse Reactions (6.1)]. The majority of patients who discontinued SAXENDA due to adverse reactions did so during the first few months of treatment. In the 160-week trial the proportions of patients who discontinued due to an adverse reaction was 13% and 6% for SAXENDA- and placebo-treated patients, respectively.

Effect of SAXENDA on Body Weight in 56-week Trials

For Study 1 and Study 2, the primary efficacy parameters were mean percent change in body weight and the percentages of patients achieving greater than or equal to 5% and 10% weight loss from baseline to week 56. For Study 3, the primary efficacy parameters were mean percent change in body weight from randomization to week 56, the percentage of patients not gaining more than 0.5% body weight from randomization (i.e., after run-in) to week 56, and the percentage of patients achieving greater than or equal to 5% weight loss from randomization to week 56. Because losing at least 5% of fasting body weight through lifestyle intervention during the 4- to 12-week run-in was a condition for their continued participation in the randomized treatment period, the results may not reflect those expected in the general population.

Table 4 presents the results for the changes in weight observed in Studies 1, 2, and 3. After 56 weeks, treatment with SAXENDA resulted in a statistically significant reduction in weight compared with placebo. Statistically significantly greater proportions of patients treated with SAXENDA achieved 5% and 10% weight loss than those treated with placebo. In Study 3, statistically significantly more patients randomized to SAXENDA than placebo had not gained more than 0.5% of body weight from randomization to week 56.

Table 4. Changes in Weight at Week 56 for Studies 1, 2, and 3

<div class="scrollingtable"><table width="98.04%"> <col width="28%"/> <col width="12%"/> <col width="13%"/> <col width="12%"/> <col width="12%"/> <col width="12%"/> <col width="11%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Study 1 (Obesity or overweight with comorbidity)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Study 2 (Type 2 diabetes with obesity or overweight)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">Study 3 (Obesity or overweight with comorbidity following at least 5% weight loss with diet)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">SAXENDA</span> </p> <p> <span class="Bold">N=2487</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">N=1244</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">SAXENDA</span> </p> <p> <span class="Bold">N=423</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">N=212</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">SAXENDA</span> </p> <p> <span class="Bold">N=212</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">N=210</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Weight </span> </p> </td><td class="Botrule Lrule Rrule" valign="middle"></td><td class="Botrule Lrule Rrule" valign="middle"></td><td class="Botrule Lrule Rrule" valign="middle"></td><td class="Botrule Lrule Rrule" valign="middle"></td><td class="Botrule Lrule Rrule" valign="middle"></td><td class="Botrule Lrule Rrule" valign="middle"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Baseline mean (SD) (kg)</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">106.2</p> <p>(21.2)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">106.2 (21.7)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">105.7</p> <p>(21.9)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">106.5</p> <p>(21.3)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">100.4</p> <p>(20.8)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">98.7</p> <p>(21.2)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Percent change from baseline (LSMean) </dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-7.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-5.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-1.7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-4.9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Difference from placebo </dd> <dt> </dt> <dd>(LSMean) (95% CI)</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-4.5<span class="Sup">*</span> </p> <p>(-5.2;-3.8)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-3.7<span class="Sup">*</span> </p> <p>(-4.7;-2.7)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-5.2<span class="Sup">*</span> </p> <p>(-6.8;-3.5)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">% of Patients losing greater than or equal to 5% body weight</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">62.3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">34.4%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">49%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">16.4%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">44.2%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">21.7%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Difference from placebo</dd> <dt> </dt> <dd>(LSMean) (95% CI)</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">27.9<span class="Sup">*</span> </p> <p>(23.9;31.9)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">32.6<span class="Sup">*</span> </p> <p>(25.1;40.1)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">22.6<span class="Sup">*</span> </p> <p>(13.9;31.3)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">% of Patients losing greater than 10% body weight</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">33.9%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">15.4%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">22.4%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5.5%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">25.4%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">6.9%</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Difference from placebo</dd> <dt> </dt> <dd>(LSMean) (95% CI)</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">18.5<span class="Sup">*</span> </p> <p>(15.2;21.7)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">16.9<span class="Sup">*</span> </p> <p>(11.7;22.1)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">18.5<span class="Sup">*</span> </p> <p>(11.7;25.3)</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> </tbody> </table></div>

SD = Standard Deviation; CI = Confidence Interval

* p < 0.0001 compared to placebo. Type 1 error was controlled across the three endpoints.

Includes all randomized subjects who had a baseline body weight measurement. All available body weight data during the 56 week treatment period are included in the analysis. In Studies 1 and 2 missing values for week 56 were handled using multiple imputations analysis. In Study 3 missing values for week 56 were handled using weighted regression analysis.

The cumulative frequency distributions of change in body weight from baseline to week 56 are shown in Figure 2 for Studies 1 and 2. One way to interpret this figure is to select a change in body weight of interest on the horizontal axis and note the corresponding proportions of patients (vertical axis) in each treatment group who achieved at least that degree of weight loss. For example, note that the vertical line arising from ‑10% in Study 1 intersects the SAXENDA and placebo curves at approximately 34% and 15%, respectively, which correspond to the values shown in Table 4.

Figure 2. Change in body weight (%) from baseline to week 56 (Study 1 on left and Study 2 on right)

The time courses of weight loss with SAXENDA and placebo from baseline through week 56 are depicted in Figure 3 and Figure 4.

Figure 3. Change from baseline (%) in body weight (Study 1 on left and Study 2 on right)

Figure 4. Change from baseline (%) in body weight during Study 3

Effect of SAXENDA on Body Weight in a 160-week Trial (Study 1, Subset of Patients with Abnormal Blood Glucose at Randomization)

The numbers and percentages of patients known to have lost greater than or equal to 5% body weight at week 56 and/or week 160 in Study 1 (patients with abnormal glucose at randomization only) are summarized in Table 5 for descriptive purposes.

<div class="scrollingtable"><table width="89.86%"> <col width="38%"/> <col width="29%"/> <col width="33%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">SAXENDA</span> </p> <p> <span class="Bold">N=1505</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">N=749</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Baseline mean body weight (SD) (kg)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">107.5 (21.6)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">107.9 (21.8)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Number (%) of patients known to lose greater than or equal to 5% body weight at 56 weeks</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">817 (56%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">182 (25%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Number (%) of patients known to lose greater than or equal to 5% body weight at 160 weeks</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">424 (28%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">102 (14%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Number (%) of patients known to lose greater than or equal to 5% body weight at both 56 weeks and 160 weeks</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">391 (26%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">74 (10%)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Number (%) of patients with weight assessment at 160 weeks</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">747 (50%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">322 (43%)</p> </td> </tr> </tbody> </table></div>

SD = Standard Deviation

Includes all randomized subjects who had a baseline body weight measurement. All available body weight data at 56 and 160 weeks are included in the analysis.

Effect of SAXENDA on Anthropometry and Cardiometabolic Parameters in 56-week Trials

Changes in waist circumference and cardiometabolic parameters with SAXENDA are shown in Table 6 for Study 1 (patients without diabetes mellitus) and Table 7 for Study 2 (patients with type 2 diabetes). Results from Study 3, which also enrolled patients without diabetes mellitus, were similar to Study 1.

<div class="scrollingtable"><table width="98.86%"> <col width="31%"/> <col width="12%"/> <col width="15%"/> <col width="11%"/> <col width="14%"/> <col width="18%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">SAXENDA</span> </p> <p> <span class="Bold">N = 2487</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">N = 1244</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Baseline</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Change from</span> </p> <p> <span class="Bold">Baseline</span> </p> <p> <span class="Bold">(LSMean<span class="Sup">1</span>)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Baseline</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Change from Baseline</span> </p> <p> <span class="Bold">(LSMean<span class="Sup">1</span>)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">SAXENDA minus </span> </p> <p> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">(LSMean)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Waist Circumference (cm)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">115</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-8.2</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">114.5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-4.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Systolic Blood Pressure (mmHg)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">123</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-4.3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">123.3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-1.5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-2.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Diastolic Blood Pressure (mmHg)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">78.7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-2.7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">78.9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-1.8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-0.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Heart Rate (bpm)<span class="Sup">2</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">71.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2.6</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">71.3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">HbA<span class="Sub">1c</span> (%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5.6</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-0.3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5.6</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-0.1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-0.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Baseline</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">% Change</span> </p> <p> <span class="Bold">from Baseline</span> </p> <p> <span class="Bold">(LSMean<span class="Sup">1</span>)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Baseline</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">% Change from Baseline</span> </p> <p> <span class="Bold">(LSMean<span class="Sup">1</span>)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Relative Difference of SAXENDA to Placebo</span> </p> <p> <span class="Bold">(LSMean)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Total Cholesterol (mg/dL)<span class="Sup">*</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">193.8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-3.2</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">194.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-0.9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-2.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">LDL Cholesterol (mg/dL)<span class="Sup">*</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">111.8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-3.1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">112.3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-0.7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-2.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">HDL Cholesterol (mg/dL)<span class="Sup">*</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">51.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2.3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">50.9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1.9</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Triglycerides (mg/dL)<span class="Sup">†</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">125.7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-13</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">128.3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-4.1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-7.1</p> </td> </tr> </tbody> </table></div>

Based on last observation carried forward method while on study drug

1 Least squares mean adjusted for treatment, country, sex, pre-diabetes status at screening, baseline BMI stratum and an interaction between pre-diabetes status at screening and BMI stratum as fixed factors, and the baseline value as covariate.

2 See Warnings and Precautions (5.5)

* Baseline value is the geometric mean

†Values are baseline median, median % change, and the Hodges-Lehmann estimate of the median treatment difference.

<div class="scrollingtable"><table width="100%"> <col width="30%"/> <col width="11%"/> <col width="14%"/> <col width="10%"/> <col width="13%"/> <col width="23%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">SAXENDA</span> </p> <p> <span class="Bold">N = 423</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">N = 212</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Baseline</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Change from Baseline</span> </p> <p> <span class="Bold">(LSMean<span class="Sup">1</span>)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Baseline</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Change From Baseline</span> </p> <p> <span class="Bold">(LSMean<span class="Sup">1</span>)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">SAXENDA minus </span> </p> <p> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">(LSMean)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Waist Circumference (cm)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">118.1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-6</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">117.3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-2.8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-3.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Systolic Blood Pressure (mmHg)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">128.9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">129.2</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-0.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-2.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Diastolic Blood Pressure (mmHg)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">79</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">79.3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-0.6</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-0.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Heart Rate (bpm)<span class="Sup">2</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">74</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">74</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-1.5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3.4 </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">HbA<span class="Sub">1c </span>(%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">7.9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-1.3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">7.9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-0.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-0.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Baseline</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">% Change from Baseline</span> </p> <p> <span class="Bold">(LSMean<span class="Sup">1</span>)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Baseline</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">% Change From Baseline</span> </p> <p> <span class="Bold">(LSMean<span class="Sup">1</span>)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Relative Difference of SAXENDA to Placebo</span> </p> <p> <span class="Bold">(LSMean)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Total Cholesterol (mg/dL)<span class="Sup">*</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">171</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-1.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">169.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-3.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">LDL Cholesterol (mg/dL)<span class="Sup">*</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">86.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">85.2</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3.3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-2.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">HDL Cholesterol (mg/dL)<span class="Sup">*</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">45.2</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4.8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">45.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1.9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2.9</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Triglycerides (mg/dL)<span class="Sup">†</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">156.2</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-14.5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">155.8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-0.7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-13.5</p> </td> </tr> </tbody> </table></div>

Based on last observation carried forward method while on study drug

1 Least squares mean adjusted for treatment, country, sex, background treatment, baseline HbA1c stratum and an interaction between background treatment and HbA1c stratum as fixed factors, and the baseline value as covariate.

2 See Warnings and Precautions (5.5)

* Baseline value is the geometric mean

†Values are baseline median, median % change, and the Hodges-Lehmann estimate of the median treatment difference.

SAXENDA was evaluated in a 56-week, double-blind, randomized, parallel group, placebo controlled multi-center trial in 251 pubertal pediatric patients aged 12 to 17 years, with BMI corresponding to 30 kg/m2 or greater for adults by international cut-off points1 and BMI of 95th percentile or greater for age and sex (NCT02918279). After a 12-week lifestyle run-in period, patients were randomized 1:1 to SAXENDA once-daily or placebo once-daily. The SAXENDA dose was titrated to 3 mg over a 4- to 8-week period based on tolerability as judged by the investigator. Escalation of the trial product was not allowed if the subject had a self-monitored plasma glucose (SMPG) < 56 mg/dL or < 70 mg/dL in the presence of symptoms of hypoglycemia during the week prior to or during the dose escalation visits. The proportion of patients who reached the 3 mg dose was 82.4%; for 8.8% of patients 2.4 mg was the maximum tolerated dose.

The mean age was 14.5 years: 40.6% of patients were male, 87.6% were White, 0.8% were Asian, 8% were Black or African American; 22.3% were of Hispanic or Latino ethnicity. The mean baseline body weight was 100.8 kg, and mean Body Mass Index (BMI) was 35.6 kg/m2.

The proportions of patients who discontinued study drug were 19.2% for the SAXENDA-treated group and 20.6% for the placebo-treated group; 10.4% of patients treated with SAXENDA and no patients treated with placebo discontinued treatment due to an adverse reaction [see Adverse Reactions (6.1)].

The primary endpoint was change in BMI SDS. At baseline, mean BMI SDS was 3.14 in the SAXENDA group and 3.20 in the placebo group. At week 56, treatment with SAXENDA resulted in statistically significant reduction in BMI SDS from baseline compared to placebo. The observed mean change in BMI SDS from baseline to week 56 was -0.23 in the SAXENDA group and -0.00 in the placebo group. The estimated treatment difference in BMI SDS reduction from baseline between SAXENDA and placebo was -0.22 with a 95% confidence interval of -0.37, -0.08; p=0.0022.

The time course of change in BMI SDS with SAXENDA and placebo from baseline through week 56 are depicted in Figure 5.

Figure 5. Change from Baseline in BMI SDS

Changes in weight and BMI with SAXENDA are shown in Table 8. Changes in waist circumference and cardiometabolic parameters with SAXENDA are shown in Table 9.

Table 8. Changes in Weight and BMI at Week 56 for Study 4 (Pediatric Patients Ages 12 to Less than 18)

<div class="scrollingtable"><table width="100%"> <col width="32%"/> <col width="19%"/> <col width="25%"/> <col width="25%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">SAXENDA</span> </p> <p> <span class="Bold">N=125</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">N=126</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">SAXENDA minus </span> </p> <p> <span class="Bold">Placebo</span> </p> </td> </tr> <tr> <td align="justify" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Body Weight</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="middle"> <dl> <dt> </dt> <dd>Baseline mean Body Weight (kg)</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">99.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">102.2</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="middle"> <dl> <dt> </dt> <dd>Mean Change from Baseline (%)</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">-2.65 </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">2.37</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">-5.01</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">BMI</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="middle"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Baseline mean BMI (kg/m<span class="Sup">2</span>)</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">35.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">35.8</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Mean Change from Baseline (%)</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">-4.29</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">0.35</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">-4.64</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Proportion of patients with greater than or equal to 5% reduction in baseline BMI at week 56 (%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">43.3%</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">18.7%</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">24.6%</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Proportion of patients with greater than or equal to 10% reduction in baseline BMI at week 56 (%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">26.1%</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">8.1%</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">18%</p> </td> </tr> </tbody> </table></div>

Full Analysis Set. For body weight and BMI, baseline values are means, changes from baseline at week 56 are estimated means (least-squares) and treatment contrasts at week 56 are estimated treatment differences. Missing observations were imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach.

Table 9. Mean Changes in Anthropometry and Cardiometabolic Parameters in Study 4 (Pediatric Patients Ages 12 to Less than 18)

<div class="scrollingtable"><table width="100%"> <col width="32%"/> <col width="11%"/> <col width="14%"/> <col width="11%"/> <col width="14%"/> <col width="16%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">SAXENDA</span> </p> <p> <span class="Bold">N = 125</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">N = 126</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Baseline</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold"> Change from Baseline</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Baseline</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Change from Baseline</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">SAXENDA minus </span> </p> <p> <span class="Bold">Placebo</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Waist Circumference (cm)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">105</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-4.35</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">107</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-1.42</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-2.93</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Systolic Blood Pressure (mmHg)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">116</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-1.21</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">117</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.84</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-2.05</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Diastolic Blood Pressure (mmHg)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">72</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.77</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">73</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-0.46</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.24</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Heart Rate (bpm)<span class="Sup">*</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">75</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.87</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">78</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-0.14</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.01</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">HbA<span class="Sub">1c</span> (%)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-0.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-0.03</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-0.06</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Baseline</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">% Change from Baseline</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Baseline</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">% Change from Baseline</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Relative Difference of SAXENDA to Placebo</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Total Cholesterol (mg/dL)<span class="Sup">**</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">154.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.84</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">152.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-0.03</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.88</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">LDL Cholesterol (mg/dL)<span class="Sup">**</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">85.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.74</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">82.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.01</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-1.27</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">HDL Cholesterol (mg/dL)<span class="Sup">**</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">42.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.14</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">42.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.33</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.81</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Triglycerides (mg/dL)<span class="Sup">**</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">109.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-0.12</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">112.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-1.35</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.23</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" colspan="6" valign="top"> <p class="First"> <span class="Sup">*</span> See <span class="Italics">Warnings and Precautions (<a href="#ID_1fbff8a9-7446-48bd-b813-1897f9784468">5.5</a>)</span> </p> </td> </tr> </tbody> </table></div>

Full Analysis Set. Baseline values are means, changes from baseline at week 56 are estimated means (least-squares) and treatment contrasts at week 56 are estimated treatment differences. Missing observations were imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach.

Liraglutide 1.8 mg (Victoza) is used in the treatment of type 2 diabetes mellitus in adults. The efficacy of liraglutide at doses below 3 mg daily has not been established for chronic weight management.

The LEADER trial (NCT01179048) randomized 9340 patients with inadequately controlled type 2 diabetes and cardiovascular disease to liraglutide 1.8 mg or placebo in addition to standard of care treatments for type 2 diabetes for a median duration of 3.5 years. Patients either were 50 years of age or older with established, stable cardiovascular, cerebrovascular, peripheral vascular disease, chronic renal failure or chronic heart failure (80% of patients), or were 60 years of age or older and had other specified risk factors of vascular disease (20% of patients).The population was 64% male, 78% White, 10% Asian and 8% Black or African American; 12% of the population was Hispanic or Latino Ethnicity.

In total, 96.8% of the patients completed the trial; vital status was known at the end of the trial for 99.7%. The primary endpoint was the time from randomization to first occurrence of a major adverse cardiovascular event (MACE) defined as: cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. No increased risk for MACE was observed with liraglutide 1.8 mg. The total number of primary component MACE endpoints was 1302 (608 [13.0%] with liraglutide 1.8 mg and 694 [14.9%] with placebo).

1. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ. 2000;320(7244):1240-3.

{ "type": "p", "children": [], "text": "1. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ. 2000;320(7244):1240-3." }

How Supplied

{ "type": "p", "children": [], "text": "\nHow Supplied\n" }

SAXENDA injection: 6 mg/mL clear, colorless solution in a 3 mL single-patient-use prefilled pen that delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg is available in the following package sizes:

{ "type": "p", "children": [], "text": "SAXENDA injection: 6 mg/mL clear, colorless solution in a 3 mL single-patient-use prefilled pen that delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg is available in the following package sizes:" }

3 x SAXENDA pen NDC 0169-2800-13

{ "type": "p", "children": [], "text": "3 x SAXENDA pen NDC 0169-2800-13 " }

5 x SAXENDA pen NDC 0169-2800-15

{ "type": "p", "children": [], "text": "5 x SAXENDA pen NDC 0169-2800-15" }

Recommended Storage

{ "type": "p", "children": [], "text": "\nRecommended Storage\n" }

Prior to first use, SAXENDA should be stored in a refrigerator between 36ºF to 46ºF (2ºC to 8ºC). Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze SAXENDA and do not use SAXENDA if it has been frozen.

{ "type": "p", "children": [], "text": "Prior to first use, SAXENDA should be stored in a refrigerator between 36ºF to 46ºF (2ºC to 8ºC). Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze SAXENDA and do not use SAXENDA if it has been frozen." }

After initial use of the SAXENDA pen, the pen can be stored for 30 days at controlled room temperature (59°F to 86°F; 15°C to 30°C) or in a refrigerator (36°F to 46°F; 2°C to 8°C). Keep the pen cap on when not in use. Protect SAXENDA from excessive heat and sunlight. Always remove and safely discard the needle after each injection and store the SAXENDA pen without an injection needle attached. This will reduce the potential for contamination, infection, and leakage while also ensuring dosing accuracy.

{ "type": "p", "children": [], "text": "After initial use of the SAXENDA pen, the pen can be stored for 30 days at controlled room temperature (59°F to 86°F; 15°C to 30°C) or in a refrigerator (36°F to 46°F; 2°C to 8°C). Keep the pen cap on when not in use. Protect SAXENDA from excessive heat and sunlight. Always remove and safely discard the needle after each injection and store the SAXENDA pen without an injection needle attached. This will reduce the potential for contamination, infection, and leakage while also ensuring dosing accuracy." }

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use)." }

Instructions

{ "type": "p", "children": [], "text": "\nInstructions\n" }

Advise patients to take SAXENDA exactly as prescribed. Instruct patients to follow the dose escalation schedule and to not take more than the recommended dose.

{ "type": "p", "children": [], "text": "Advise patients to take SAXENDA exactly as prescribed. Instruct patients to follow the dose escalation schedule and to not take more than the recommended dose." }

Instruct adult patients to discontinue SAXENDA if they have not achieved 4% weight loss by 16 weeks of treatment. Instruct pediatric patients 12 years of age and older to discontinue SAXENDA if they have not achieved a BMI reduction of 1% from baseline after 12 weeks on the maintenance dose.

{ "type": "p", "children": [], "text": "Instruct adult patients to discontinue SAXENDA if they have not achieved 4% weight loss by 16 weeks of treatment. Instruct pediatric patients 12 years of age and older to discontinue SAXENDA if they have not achieved a BMI reduction of 1% from baseline after 12 weeks on the maintenance dose. " }

Risk of Thyroid C-cell Tumors

{ "type": "p", "children": [], "text": "\nRisk of Thyroid C-cell Tumors\n" }

Inform patients that liraglutide causes benign and malignant thyroid C-cell tumors in mice and rats and that the human relevance of this finding has not been determined. Counsel patients to report symptoms of thyroid tumors (e.g., a lump in the neck, hoarseness, dysphagia or dyspnea) to their health care provider [see Boxed Warning, Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Inform patients that liraglutide causes benign and malignant thyroid C-cell tumors in mice and rats and that the human relevance of this finding has not been determined. Counsel patients to report symptoms of thyroid tumors (e.g., a lump in the neck, hoarseness, dysphagia or dyspnea) to their health care provider [see Boxed Warning, Warnings and Precautions (5.1)].\n" }

Acute Pancreatitis

{ "type": "p", "children": [], "text": "\nAcute Pancreatitis\n" }

Inform patients of the potential risk for acute pancreatitis and its symptoms: severe abdominal pain that may radiate to the back, and which may or may not be accompanied by vomiting. Instruct patients to discontinue SAXENDA promptly and contact their healthcare provider if pancreatitis is suspected [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Inform patients of the potential risk for acute pancreatitis and its symptoms: severe abdominal pain that may radiate to the back, and which may or may not be accompanied by vomiting. Instruct patients to discontinue SAXENDA promptly and contact their healthcare provider if pancreatitis is suspected [see Warnings and Precautions (5.2)].\n" }

Acute Gallbladder Disease

{ "type": "p", "children": [], "text": "\nAcute Gallbladder Disease\n" }

Inform patients of the risk of acute gallbladder disease. Advise patients that substantial or rapid weight loss can increase the risk of gallbladder disease, but that gallbladder disease may also occur in the absence of substantial or rapid weight loss. Instruct patients to contact their healthcare provider for appropriate clinical follow-up if gallbladder disease is suspected [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Inform patients of the risk of acute gallbladder disease. Advise patients that substantial or rapid weight loss can increase the risk of gallbladder disease, but that gallbladder disease may also occur in the absence of substantial or rapid weight loss. Instruct patients to contact their healthcare provider for appropriate clinical follow-up if gallbladder disease is suspected [see Warnings and Precautions (5.3)]." }

Hypoglycemia

{ "type": "p", "children": [], "text": "\nHypoglycemia\n" }

Inform pediatric patients of the risk of hypoglycemia and educate all patients on the signs and symptoms of hypoglycemia. Inform adult patients with type 2 diabetes mellitus on an insulin secretagogue (e.g., sulfonylurea) or insulin that they may have an increased risk of hypoglycemia when using SAXENDA and to report signs and/or symptoms of hypoglycemia to their healthcare provider [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "Inform pediatric patients of the risk of hypoglycemia and educate all patients on the signs and symptoms of hypoglycemia. Inform adult patients with type 2 diabetes mellitus on an insulin secretagogue (e.g., sulfonylurea) or insulin that they may have an increased risk of hypoglycemia when using SAXENDA and to report signs and/or symptoms of hypoglycemia to their healthcare provider [see Warnings and Precautions (5.4)]." }

Heart Rate Increase

{ "type": "p", "children": [], "text": "\nHeart Rate Increase\n" }

Inform patients to report symptoms of sustained periods of heart pounding or racing while at rest to their healthcare provider. Discontinue SAXENDA in patients who experience a sustained increase in resting heart rate [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "Inform patients to report symptoms of sustained periods of heart pounding or racing while at rest to their healthcare provider. Discontinue SAXENDA in patients who experience a sustained increase in resting heart rate [see Warnings and Precautions (5.5)]." }

Acute Kidney Injury Due to Volume Depletion

{ "type": "p", "children": [], "text": "\nAcute Kidney Injury Due to Volume Depletion\n" }

Inform patients of the potential risk of acute kidney injury due to dehydration associated with gastrointestinal

{ "type": "p", "children": [], "text": "Inform patients of the potential risk of acute kidney injury due to dehydration associated with gastrointestinal" }

adverse reactions. Advise patients to take precautions to avoid fluid depletion. Inform patients of the signs and symptoms of acute kidney injury and instruct them to promptly report any of these signs or symptoms or

{ "type": "p", "children": [], "text": "adverse reactions. Advise patients to take precautions to avoid fluid depletion. Inform patients of the signs and symptoms of acute kidney injury and instruct them to promptly report any of these signs or symptoms or" }

persistent (or extended) nausea, vomiting, and diarrhea to their healthcare provider [see Warnings and Precautions (5.6)].

{ "type": "p", "children": [], "text": "persistent (or extended) nausea, vomiting, and diarrhea to their healthcare provider [see Warnings and Precautions (5.6)].\n" }

Severe Gastrointestinal Adverse Reactions

{ "type": "p", "children": [], "text": "\nSevere Gastrointestinal Adverse Reactions\n" }

Inform patients of the potential risk of severe gastrointestinal adverse reactions. Instruct patients to contact their healthcare provider if they have severe or persistent gastrointestinal symptoms [see Warnings and Precautions

{ "type": "p", "children": [], "text": "Inform patients of the potential risk of severe gastrointestinal adverse reactions. Instruct patients to contact their healthcare provider if they have severe or persistent gastrointestinal symptoms [see Warnings and Precautions\n" }

(5.7)].

{ "type": "p", "children": [], "text": "\n(5.7)].\n" }

Hypersensitivity Reactions

{ "type": "p", "children": [], "text": "\nHypersensitivity Reactions\n" }

Inform patients that serious hypersensitivity reactions have been reported during postmarketing use of SAXENDA. Advise patients on the symptoms of hypersensitivity reactions and instruct them to stop taking SAXENDA and seek medical advice promptly if such symptoms occur [see Warnings and Precautions (5.8)].

{ "type": "p", "children": [], "text": "Inform patients that serious hypersensitivity reactions have been reported during postmarketing use of SAXENDA. Advise patients on the symptoms of hypersensitivity reactions and instruct them to stop taking SAXENDA and seek medical advice promptly if such symptoms occur [see Warnings and Precautions (5.8)]." }

Suicidal Behavior and Ideation

{ "type": "p", "children": [], "text": "\nSuicidal Behavior and Ideation \n" }

Advise patients to report emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Inform patients that if they experience suicidal thoughts or behaviors, they should stop taking SAXENDA [see Warnings and Precautions (5.9)].

{ "type": "p", "children": [], "text": "Advise patients to report emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Inform patients that if they experience suicidal thoughts or behaviors, they should stop taking SAXENDA [see Warnings and Precautions (5.9)].\n" }

Pulmonary Aspiration During General Anesthesia or Deep Sedation

{ "type": "p", "children": [], "text": "\nPulmonary Aspiration During General Anesthesia or Deep Sedation \n" }

Inform patients that SAXENDA may cause their stomach to empty more slowly which may lead to complications with anesthesia or deep sedation during planned surgeries or procedures. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking SAXENDA [see Warnings and Precautions (5.10)].

{ "type": "p", "children": [], "text": "Inform patients that SAXENDA may cause their stomach to empty more slowly which may lead to complications with anesthesia or deep sedation during planned surgeries or procedures. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking SAXENDA [see Warnings and Precautions (5.10)].\n" }

Never Share a SAXENDA Pen Between Patients

{ "type": "p", "children": [], "text": "\nNever Share a SAXENDA Pen Between Patients\n" }

Inform patients that they should never share a SAXENDA pen with another person, even if the needle is changed. Sharing of the pen between patients may pose a risk of transmission of infection.

{ "type": "p", "children": [], "text": "Inform patients that they should never share a SAXENDA pen with another person, even if the needle is changed. Sharing of the pen between patients may pose a risk of transmission of infection." }

SAXENDA® and VICTOZA® are registered trademarks of Novo Nordisk A/S.

{ "type": "p", "children": [], "text": "\nSAXENDA® and VICTOZA® are registered trademarks of Novo Nordisk A/S.\n" }

PATENT Information: http://novonordisk-us.com/products/product-patents.html

{ "type": "p", "children": [], "text": "PATENT Information: http://novonordisk-us.com/products/product-patents.html" }

© 2025 Novo Nordisk

{ "type": "p", "children": [], "text": "© 2025 Novo Nordisk" }

Manufactured by: Novo Nordisk A/SDK-2880 Bagsvaerd, Denmark

{ "type": "p", "children": [], "text": "Manufactured by: Novo Nordisk A/SDK-2880 Bagsvaerd, Denmark" }

For information about SAXENDA contact:Novo Nordisk Inc.800 Scudders Mill RoadPlainsboro, NJ 08536

{ "type": "p", "children": [], "text": "For information about SAXENDA contact:Novo Nordisk Inc.800 Scudders Mill RoadPlainsboro, NJ 08536" }

1-844-363-4448

{ "type": "p", "children": [], "text": "1-844-363-4448" }

<div class="scrollingtable"><table width="540pt"> <col width="19%"/> <col width="12%"/> <col width="16%"/> <col width="4%"/> <col width="2%"/> <col width="21%"/> <col width="27%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="7" valign="top"> <p class="First"> <span class="Bold">MEDICATION GUIDE</span> </p> <p> <span class="Bold">SAXENDA (sax-end-ah)</span> </p> <p> <span class="Bold">(liraglutide) injection, for subcutaneous use</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">What is the most important information I should know about SAXENDA?</span> </p> <p> <span class="Bold">Serious side effects may happen in people who take SAXENDA, including:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Possible thyroid tumors, including cancer. </span>Tell your healthcare provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. In studies with rats and mice, SAXENDA and medicines that work like SAXENDA caused thyroid tumors, including thyroid cancer. It is not known if SAXENDA will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people. </dd> <dt>•</dt> <dd> <span class="Bold">Do not use SAXENDA</span> if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC), or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">What is SAXENDA?</span> </p> <p>SAXENDA is an injectable prescription medicine used for adults with obesity or overweight (excess weight) who also have weight related medical problems, and children aged 12 to 17 years with a body weight above 132 pounds (60 kg) and obesity to help them lose weight and keep the weight off.</p> <dl> <dt>•</dt> <dd>SAXENDA should be used with a reduced calorie diet and increased physical activity.</dd> <dt>•</dt> <dd>SAXENDA is not recommended for people who also take liraglutide or other medicines called glucagon-like peptide-1 (GLP-1) receptor agonists.</dd> <dt>•</dt> <dd>It is not known if SAXENDA is safe and effective in children under 12 years of age.</dd> <dt>•</dt> <dd>It is not known if SAXENDA is safe and effective in children aged 12 to 17 years with type 2 diabetes.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Who should not use SAXENDA?</span> </p> <p> <span class="Bold">Do not use SAXENDA if:</span> </p> <dl> <dt>•</dt> <dd>you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC) or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).</dd> <dt>•</dt> <dd>you have had a serious allergic reaction to liraglutide or any of the ingredients in SAXENDA. See the end of this Medication Guide for a complete list of ingredients in SAXENDA. See “<span class="Bold">What are the possible side effects of SAXENDA?</span>” for symptoms of a serious allergic reaction.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Before taking SAXENDA, tell your healthcare provider about all of your medical conditions, including if you:</span> </p> <dl> <dt>•</dt> <dd>have or have had problems with your pancreas.</dd> <dt>•</dt> <dd>have severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems with digesting food.</dd> <dt>•</dt> <dd>are scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation).</dd> <dt>•</dt> <dd>have or have had depression or suicidal thoughts, or mental health issues.</dd> <dt>•</dt> <dd>are breastfeeding or plan to breastfeed. It is not known if SAXENDA passes into your breast milk. You and your healthcare provider should decide if you will use SAXENDA or breastfeed.</dd> </dl> <p> <span class="Bold">Tell your healthcare provider about all the medicines you take</span> including prescription, over-the-counter medicines, vitamins, and herbal supplements. SAXENDA may affect the way some medicines work and some other medicines may affect the way SAXENDA works.</p> <p>Tell your healthcare provider if you take diabetes medicines, especially insulin and sulfonylurea medicines. Talk with your healthcare provider if you are not sure if you take any of these medicines.</p> <p>Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">How should I use SAXENDA?</span> </p> <dl> <dt>•</dt> <dd>Read the Instructions for Use that comes with SAXENDA.</dd> <dt>•</dt> <dd>Use SAXENDA exactly as your healthcare provider tells you to.</dd> <dt>•</dt> <dd> <span class="Bold">Your healthcare provider should show you how to use SAXENDA before you use it for the first time.</span> </dd> <dt>•</dt> <dd>Use SAXENDA with a reduced-calorie diet and increased physical activity.</dd> <dt>•</dt> <dd>SAXENDA is injected under the skin (subcutaneously) in your stomach area (abdomen), upper leg (thigh), or upper arm. <span class="Bold">Do not </span>inject into a muscle (intramuscularly) or vein (intravenously).</dd> <dt>•</dt> <dd> <span class="Bold">SAXENDA is injected 1 time each day, at any time during the day.</span> </dd> <dt>•</dt> <dd>Start SAXENDA with 0.6 mg per day in your first week. In your second week, increase your daily dose to 1.2 mg. In the third week, increase your daily dose to 1.8 mg. In the fourth week, increase your daily dose to 2.4 mg and in the fifth week onwards, increase your daily dose to the full dose of 3 mg. After that, do not change your dose unless your healthcare provider tells you to. Children may reduce their dose to 2.4 mg daily if the maximum dose is not tolerated.</dd> <dt>•</dt> <dd>If you miss your daily dose of SAXENDA, just take your next daily dose as usual on the following day. Do not take an extra dose of SAXENDA or increase your dose on the following day to make up for your missed dose. If you miss your dose of SAXENDA for <span class="Bold">3 days or more</span>, call your healthcare provider to talk about how to restart your treatment.</dd> <dt>•</dt> <dd>SAXENDA may be taken with or without food.</dd> <dt>•</dt> <dd>Change (rotate) your injection site with each injection.<span class="Bold"> Do not</span> use the same site for each injection.</dd> <dt>•</dt> <dd> <span class="Bold">Do not share your SAXENDA pen with other people, even if the needle has been changed.</span> You may give other people a serious infection or get a serious infection from them.</dd> <dt>•</dt> <dd>If you take too much SAXENDA, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.</dd> <dt>•</dt> <dd>Throw away the used SAXENDA pen after 30 days.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">What are the possible side effects of SAXENDA?</span> </p> <p> <span class="Bold">SAXENDA may cause serious side effects, including:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">See “What is the most important information I should know about SAXENDA?”</span> </dd> <dt>•</dt> <dd> <span class="Bold">inflammation of the pancreas</span> (<span class="Bold">pancreatitis). </span>Stop using SAXENDA and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your stomach area (abdomen) to your back.</dd> <dt>•</dt> <dd> <span class="Bold">increased risk of low blood sugar (hypoglycemia) in adults with type 2 diabetes, especially those who also take medicines to treat type 2 diabetes mellitus such as an insulin or a sulfonylureas and in children who are 12 years of age and older without type 2 diabetes mellitus.</span> Low blood sugar in patients with adults with type 2 diabetes and in children without type 2 diabetes mellitus who receive SAXENDA can be both a serious and common side effect. Talk to your healthcare provider about how to recognize and treat low blood sugar. You should check your blood sugar before you start taking SAXENDA and while you take SAXENDA.</dd> </dl> <p> <span class="Bold">Signs and symptoms of low blood sugar may include:</span> </p> </td> </tr> <tr> <td class="Botrule Lrule" colspan="2" valign="top"> <dl> <dt> </dt> <dd> <dl> <dt>o</dt> <dd>dizziness or light-headedness</dd> </dl> </dd> <dt>o</dt> <dd>sweating</dd> <dt>o</dt> <dd>confusion or drowsiness</dd> <dt>o</dt> <dd>headache</dd> </dl> </td><td class="Botrule Toprule" colspan="2" valign="top"> <dl> <dt>o</dt> <dd>blurred vision</dd> <dt>o</dt> <dd>slurred speech</dd> <dt>o</dt> <dd>shakiness</dd> <dt>o</dt> <dd>fast heartbeat</dd> </dl> </td><td class="Botrule Rrule Toprule" colspan="3" valign="top"> <dl> <dt>o</dt> <dd>anxiety, irritability, or mood changes</dd> <dt>o</dt> <dd>hunger </dd> <dt>o</dt> <dd>weakness</dd> <dt>o</dt> <dd>feeling jittery</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <dl> <dt> </dt> <dd>Talk to your healthcare provider about how to recognize and treat low blood sugar. You should check your blood sugar before you start taking SAXENDA and while you take SAXENDA.</dd> <dt>•</dt> <dd> <span class="Bold">increased heart rate. </span>SAXENDA can increase your heart rate while you are at rest. Your healthcare provider should check your heart rate while you take SAXENDA. Tell your healthcare provider if you feel your heart racing or pounding in your chest and it lasts for several minutes.</dd> <dt>•</dt> <dd> <span class="Bold">dehydration leading to kidney problems. </span>Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration) which may cause kidney problems. It is important for you to drink fluids to help reduce your chance of dehydration. Tell your healthcare provider right away if you have nausea, vomiting, or diarrhea that does not go away.</dd> <dt>•</dt> <dd> <span class="Bold">severe stomach problems</span>. Stomach problems, sometimes severe, have been reported in people who use SAXENDA. Tell your healthcare provider if you have stomach problems that are severe or will not go away.</dd> <dt>•</dt> <dd> <span class="Bold">serious allergic reactions.</span> Stop using SAXENDA, and get medical help right away if you have any symptoms of a serious allergic reaction including:</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule" colspan="3" valign="top"> <dl> <dt>o</dt> <dd>swelling of your face, lips, tongue, or throat</dd> <dt>o</dt> <dd>problems breathing or swallowing<dl> <dt>o</dt> <dd>severe rash or itching</dd> </dl> </dd> </dl> </td><td class="Botrule Rrule Toprule" colspan="4" valign="top"> <dl> <dt>o</dt> <dd>fainting or feeling dizzy</dd> <dt>o</dt> <dd>very rapid heartbeat</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">gallbladder problems.</span> SAXENDA may cause gallbladder problems including gallstones. Some gallbladder problems need surgery. Call your healthcare provider if you have any of the following symptoms:</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule" colspan="3" valign="top"> <dl> <dt>o</dt> <dd>pain in your upper stomach (abdomen)</dd> <dt>o</dt> <dd>fever</dd> </dl> </td><td class="Botrule Rrule Toprule" colspan="4" valign="top"> <dl> <dt>o</dt> <dd>yellowing of your skin or eyes (jaundice)</dd> <dt>o</dt> <dd>clay-colored stools</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">depression or thoughts of suicide.</span> You should pay attention to any mental changes, especially sudden changes, in your mood, behaviors, thoughts, or feelings. Call your healthcare provider right away if you have any mental changes that are new, worse, or worry you.</dd> <dt>•</dt> <dd> <span class="Bold">food or liquid getting into the lungs during surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). </span>SAXENDA may increase the chance of food getting into your lungs during surgery or other procedures. Tell all your healthcare providers that you are taking SAXENDA before you are scheduled to have surgery or other procedures.</dd> <dt> </dt> <dd> <span class="Bold">The most common side effects of SAXENDA in adults include:</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <dl> <dt>•</dt> <dd>nausea</dd> <dt>•</dt> <dd>diarrhea</dd> <dt>•</dt> <dd>constipation</dd> <dt>•</dt> <dd>vomiting</dd> </dl> </td><td class="Botrule Toprule" colspan="4" valign="top"> <dl> <dt>•</dt> <dd>injection site reaction</dd> <dt>•</dt> <dd>low blood sugar (hypoglycemia)</dd> <dt>•</dt> <dd>headache</dd> <dt>•</dt> <dd>upset stomach (dyspepsia)</dd> </dl> </td><td class="Botrule Toprule" valign="top"> <dl> <dt>•</dt> <dd>tiredness (fatigue)</dd> <dt>•</dt> <dd>dizziness</dd> <dt>•</dt> <dd>stomach pain</dd> </dl> </td><td class="Botrule Rrule Toprule" valign="top"> <dl> <dt>•</dt> <dd>change in enzyme (lipase) levels in your blood</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First">Additional common side effects in children are fever and gastroenteritis</p> <dl> <dt> </dt> <dd>Talk to your healthcare provider if you have any side effect that bothers you or that does not go away.</dd> <dt> </dt> <dd>These are not all the possible side effects of SAXENDA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</dd> </dl> <p> <span class="Bold">Keep your SAXENDA pen, pen needles, and all medicines out of the reach of children.</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">General information about the safe and effective use of SAXENDA.</span> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use SAXENDA for a condition for which it was not prescribed. Do not give SAXENDA to other people, even if they have the same symptoms that you have. It may harm them.</p> <p>You can ask your pharmacist or healthcare provider for information about SAXENDA that is written for health professionals.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" colspan="7" valign="top"> <p class="First"> <span class="Bold">What are the ingredients in SAXENDA?</span> </p> <p> <span class="Bold">Active ingredient:</span> liraglutide</p> <p> <span class="Bold">Inactive ingredients: </span>disodium phosphate dihydrate, propylene glycol, phenol and water for injection. Hydrochloric acid or sodium hydroxide may be added to adjust the pH.</p> <span class="Bold"><a name="id-542595253"></a><img alt="qr-code" src="/dailymed/image.cfm?name=image-44.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></span> <p>Manufactured by: Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark.</p> <p>For information about SAXENDA go to www.SAXENDA.com or contact: Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ 08536 1-844-363-4448</p> <p> <span class="Italics">SAXENDA<span class="Sup">®</span>, VICTOZA<span class="Sup">®</span>, and NovoFine<span class="Sup">® </span>are registered trademarks of Novo Nordisk A/S.</span> </p> <p>PATENT Information: http://novonordisk-us.com/products/product-patents.html</p> <p>© 2025 Novo Nordisk</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"540pt\">\n<col width=\"19%\"/>\n<col width=\"12%\"/>\n<col width=\"16%\"/>\n<col width=\"4%\"/>\n<col width=\"2%\"/>\n<col width=\"21%\"/>\n<col width=\"27%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"7\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">MEDICATION GUIDE</span>\n</p>\n<p>\n<span class=\"Bold\">SAXENDA (sax-end-ah)</span>\n</p>\n<p>\n<span class=\"Bold\">(liraglutide) injection, for subcutaneous use</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"7\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information I should know about SAXENDA?</span>\n</p>\n<p>\n<span class=\"Bold\">Serious side effects may happen in people who take SAXENDA, including:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Possible thyroid tumors, including cancer. </span>Tell your healthcare provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. In studies with rats and mice, SAXENDA and medicines that work like SAXENDA caused thyroid tumors, including thyroid cancer. It is not known if SAXENDA will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people. </dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not use SAXENDA</span> if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC), or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). </dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"7\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is SAXENDA?</span>\n</p>\n<p>SAXENDA is an injectable prescription medicine used for adults with obesity or overweight (excess weight) who also have weight related medical problems, and children aged 12 to 17 years with a body weight above 132 pounds (60 kg) and obesity to help them lose weight and keep the weight off.</p>\n<dl>\n<dt>•</dt>\n<dd>SAXENDA should be used with a reduced calorie diet and increased physical activity.</dd>\n<dt>•</dt>\n<dd>SAXENDA is not recommended for people who also take liraglutide or other medicines called glucagon-like peptide-1 (GLP-1) receptor agonists.</dd>\n<dt>•</dt>\n<dd>It is not known if SAXENDA is safe and effective in children under 12 years of age.</dd>\n<dt>•</dt>\n<dd>It is not known if SAXENDA is safe and effective in children aged 12 to 17 years with type 2 diabetes.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"7\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Who should not use SAXENDA?</span>\n</p>\n<p>\n<span class=\"Bold\">Do not use SAXENDA if:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC) or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).</dd>\n<dt>•</dt>\n<dd>you have had a serious allergic reaction to liraglutide or any of the ingredients in SAXENDA. See the end of this Medication Guide for a complete list of ingredients in SAXENDA. See “<span class=\"Bold\">What are the possible side effects of SAXENDA?</span>” for symptoms of a serious allergic reaction.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"7\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Before taking SAXENDA, tell your healthcare provider about all of your medical conditions, including if you:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>have or have had problems with your pancreas.</dd>\n<dt>•</dt>\n<dd>have severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems with digesting food.</dd>\n<dt>•</dt>\n<dd>are scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation).</dd>\n<dt>•</dt>\n<dd>have or have had depression or suicidal thoughts, or mental health issues.</dd>\n<dt>•</dt>\n<dd>are breastfeeding or plan to breastfeed. It is not known if SAXENDA passes into your breast milk. You and your healthcare provider should decide if you will use SAXENDA or breastfeed.</dd>\n</dl>\n<p>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take</span> including prescription, over-the-counter medicines, vitamins, and herbal supplements. SAXENDA may affect the way some medicines work and some other medicines may affect the way SAXENDA works.</p>\n<p>Tell your healthcare provider if you take diabetes medicines, especially insulin and sulfonylurea medicines. Talk with your healthcare provider if you are not sure if you take any of these medicines.</p>\n<p>Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"7\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I use SAXENDA?</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Read the Instructions for Use that comes with SAXENDA.</dd>\n<dt>•</dt>\n<dd>Use SAXENDA exactly as your healthcare provider tells you to.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Your healthcare provider should show you how to use SAXENDA before you use it for the first time.</span>\n</dd>\n<dt>•</dt>\n<dd>Use SAXENDA with a reduced-calorie diet and increased physical activity.</dd>\n<dt>•</dt>\n<dd>SAXENDA is injected under the skin (subcutaneously) in your stomach area (abdomen), upper leg (thigh), or upper arm. <span class=\"Bold\">Do not </span>inject into a muscle (intramuscularly) or vein (intravenously).</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">SAXENDA is injected 1 time each day, at any time during the day.</span>\n</dd>\n<dt>•</dt>\n<dd>Start SAXENDA with 0.6 mg per day in your first week. In your second week, increase your daily dose to 1.2 mg. In the third week, increase your daily dose to 1.8 mg. In the fourth week, increase your daily dose to 2.4 mg and in the fifth week onwards, increase your daily dose to the full dose of 3 mg. After that, do not change your dose unless your healthcare provider tells you to. Children may reduce their dose to 2.4 mg daily if the maximum dose is not tolerated.</dd>\n<dt>•</dt>\n<dd>If you miss your daily dose of SAXENDA, just take your next daily dose as usual on the following day. Do not take an extra dose of SAXENDA or increase your dose on the following day to make up for your missed dose. If you miss your dose of SAXENDA for <span class=\"Bold\">3 days or more</span>, call your healthcare provider to talk about how to restart your treatment.</dd>\n<dt>•</dt>\n<dd>SAXENDA may be taken with or without food.</dd>\n<dt>•</dt>\n<dd>Change (rotate) your injection site with each injection.<span class=\"Bold\"> Do not</span> use the same site for each injection.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not share your SAXENDA pen with other people, even if the needle has been changed.</span> You may give other people a serious infection or get a serious infection from them.</dd>\n<dt>•</dt>\n<dd>If you take too much SAXENDA, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.</dd>\n<dt>•</dt>\n<dd>Throw away the used SAXENDA pen after 30 days.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"7\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of SAXENDA?</span>\n</p>\n<p>\n<span class=\"Bold\">SAXENDA may cause serious side effects, including:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">See “What is the most important information I should know about SAXENDA?”</span>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">inflammation of the pancreas</span> (<span class=\"Bold\">pancreatitis). </span>Stop using SAXENDA and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your stomach area (abdomen) to your back.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">increased risk of low blood sugar (hypoglycemia) in adults with type 2 diabetes, especially those who also take medicines to treat type 2 diabetes mellitus such as an insulin or a sulfonylureas and in children who are 12 years of age and older without type 2 diabetes mellitus.</span> Low blood sugar in patients with adults with type 2 diabetes and in children without type 2 diabetes mellitus who receive SAXENDA can be both a serious and common side effect. Talk to your healthcare provider about how to recognize and treat low blood sugar. You should check your blood sugar before you start taking SAXENDA and while you take SAXENDA.</dd>\n</dl>\n<p>\n<span class=\"Bold\">Signs and symptoms of low blood sugar may include:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt> </dt>\n<dd>\n<dl>\n<dt>o</dt>\n<dd>dizziness or light-headedness</dd>\n</dl>\n</dd>\n<dt>o</dt>\n<dd>sweating</dd>\n<dt>o</dt>\n<dd>confusion or drowsiness</dd>\n<dt>o</dt>\n<dd>headache</dd>\n</dl>\n</td><td class=\"Botrule Toprule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>blurred vision</dd>\n<dt>o</dt>\n<dd>slurred speech</dd>\n<dt>o</dt>\n<dd>shakiness</dd>\n<dt>o</dt>\n<dd>fast heartbeat</dd>\n</dl>\n</td><td class=\"Botrule Rrule Toprule\" colspan=\"3\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>anxiety, irritability, or mood changes</dd>\n<dt>o</dt>\n<dd>hunger </dd>\n<dt>o</dt>\n<dd>weakness</dd>\n<dt>o</dt>\n<dd>feeling jittery</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"7\" valign=\"top\">\n<dl>\n<dt> </dt>\n<dd>Talk to your healthcare provider about how to recognize and treat low blood sugar. You should check your blood sugar before you start taking SAXENDA and while you take SAXENDA.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">increased heart rate. </span>SAXENDA can increase your heart rate while you are at rest. Your healthcare provider should check your heart rate while you take SAXENDA. Tell your healthcare provider if you feel your heart racing or pounding in your chest and it lasts for several minutes.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">dehydration leading to kidney problems. </span>Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration) which may cause kidney problems. It is important for you to drink fluids to help reduce your chance of dehydration. Tell your healthcare provider right away if you have nausea, vomiting, or diarrhea that does not go away.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">severe stomach problems</span>. Stomach problems, sometimes severe, have been reported in people who use SAXENDA. Tell your healthcare provider if you have stomach problems that are severe or will not go away.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">serious allergic reactions.</span> Stop using SAXENDA, and get medical help right away if you have any symptoms of a serious allergic reaction including:</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule\" colspan=\"3\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>swelling of your face, lips, tongue, or throat</dd>\n<dt>o</dt>\n<dd>problems breathing or swallowing<dl>\n<dt>o</dt>\n<dd>severe rash or itching</dd>\n</dl>\n</dd>\n</dl>\n</td><td class=\"Botrule Rrule Toprule\" colspan=\"4\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>fainting or feeling dizzy</dd>\n<dt>o</dt>\n<dd>very rapid heartbeat</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"7\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">gallbladder problems.</span> SAXENDA may cause gallbladder problems including gallstones. Some gallbladder problems need surgery. Call your healthcare provider if you have any of the following symptoms:</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule\" colspan=\"3\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>pain in your upper stomach (abdomen)</dd>\n<dt>o</dt>\n<dd>fever</dd>\n</dl>\n</td><td class=\"Botrule Rrule Toprule\" colspan=\"4\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>yellowing of your skin or eyes (jaundice)</dd>\n<dt>o</dt>\n<dd>clay-colored stools</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"7\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">depression or thoughts of suicide.</span> You should pay attention to any mental changes, especially sudden changes, in your mood, behaviors, thoughts, or feelings. Call your healthcare provider right away if you have any mental changes that are new, worse, or worry you.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">food or liquid getting into the lungs during surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). </span>SAXENDA may increase the chance of food getting into your lungs during surgery or other procedures. Tell all your healthcare providers that you are taking SAXENDA before you are scheduled to have surgery or other procedures.</dd>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">The most common side effects of SAXENDA in adults include:</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>nausea</dd>\n<dt>•</dt>\n<dd>diarrhea</dd>\n<dt>•</dt>\n<dd>constipation</dd>\n<dt>•</dt>\n<dd>vomiting</dd>\n</dl>\n</td><td class=\"Botrule Toprule\" colspan=\"4\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>injection site reaction</dd>\n<dt>•</dt>\n<dd>low blood sugar (hypoglycemia)</dd>\n<dt>•</dt>\n<dd>headache</dd>\n<dt>•</dt>\n<dd>upset stomach (dyspepsia)</dd>\n</dl>\n</td><td class=\"Botrule Toprule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>tiredness (fatigue)</dd>\n<dt>•</dt>\n<dd>dizziness</dd>\n<dt>•</dt>\n<dd>stomach pain</dd>\n</dl>\n</td><td class=\"Botrule Rrule Toprule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>change in enzyme (lipase) levels in your blood</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"7\" valign=\"top\">\n<p class=\"First\">Additional common side effects in children are fever and gastroenteritis</p>\n<dl>\n<dt> </dt>\n<dd>Talk to your healthcare provider if you have any side effect that bothers you or that does not go away.</dd>\n<dt> </dt>\n<dd>These are not all the possible side effects of SAXENDA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</dd>\n</dl>\n<p>\n<span class=\"Bold\">Keep your SAXENDA pen, pen needles, and all medicines out of the reach of children.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"7\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of SAXENDA.</span>\n</p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use SAXENDA for a condition for which it was not prescribed. Do not give SAXENDA to other people, even if they have the same symptoms that you have. It may harm them.</p>\n<p>You can ask your pharmacist or healthcare provider for information about SAXENDA that is written for health professionals.</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"7\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in SAXENDA?</span>\n</p>\n<p>\n<span class=\"Bold\">Active ingredient:</span> liraglutide</p>\n<p>\n<span class=\"Bold\">Inactive ingredients: </span>disodium phosphate dihydrate, propylene glycol, phenol and water for injection. Hydrochloric acid or sodium hydroxide may be added to adjust the pH.</p>\n<span class=\"Bold\"><a name=\"id-542595253\"></a><img alt=\"qr-code\" src=\"/dailymed/image.cfm?name=image-44.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></span>\n<p>Manufactured by: Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark.</p>\n<p>For information about SAXENDA go to www.SAXENDA.com or contact: Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ 08536 1-844-363-4448</p>\n<p>\n<span class=\"Italics\">SAXENDA<span class=\"Sup\">®</span>, VICTOZA<span class=\"Sup\">®</span>, and NovoFine<span class=\"Sup\">® </span>are registered trademarks of Novo Nordisk A/S.</span>\n</p>\n<p>PATENT Information: http://novonordisk-us.com/products/product-patents.html</p>\n<p>© 2025 Novo Nordisk</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 05/2025

{ "type": "p", "children": [], "text": "This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 05/2025" }

{ "type": "", "children": [], "text": "" }

<div class="scrollingtable"><table width="109.7%"> <col width="55%"/> <col width="45%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Step 1. Prepare your pen with a new needle</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Wash your hands </span>with soap and water.</dd> <dt>•</dt> <dd> <span class="Bold">Check the name and colored label </span>of your pen, to make sure that it contains Saxenda. This is especially important if you take more than 1 type of medicine.</dd> <dt>•</dt> <dd> <span class="Bold">Pull off the pen cap.</span> </dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id1293942579"></a><img alt="fig-a" src="/dailymed/image.cfm?name=image-05.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Check that Saxenda in your pen is clear</span> and colorless. <br/>Look through the pen window. If Saxenda looks cloudy, do not use the pen.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-1158379815"></a><img alt="fig-b" src="/dailymed/image.cfm?name=image-06.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Take a new needle,</span> and tear off the paper tab.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-1889567842"></a><img alt="fig-c" src="/dailymed/image.cfm?name=image-07.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Push the needle straight onto the pen. Turn until it is on tight.</span> </dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-1391882563"></a><img alt="fig-d" src="/dailymed/image.cfm?name=image-08.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Pull off the outer needle cap.</span> Do not throw it away.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id878668504"></a><img alt="fig-e" src="/dailymed/image.cfm?name=image-11.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Pull off the inner needle cap </span>and throw it away. <br/>A drop of Saxenda may appear at the needle tip. This is normal, but you must still check the Saxenda flow, if you use a new pen for the first time. </dd> </dl> <p class="First"> <a name="id1253545431"></a><img alt="note " src="/dailymed/image.cfm?name=image-13.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/><span class="Bold">Always use a new needle for each injection.</span> </p> <p> This will prevent contamination, infection, leakage of Saxenda,</p> <p> and blocked needles leading to the wrong dose. <br/> <span class="Bold"> Never use a bent or damaged needle.</span> </p> <p> <a name="id-1321036061"></a><img alt="info" src="/dailymed/image.cfm?name=image-14.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/><span class="Bold"> Do not attach a new needle</span> to your pen until you are ready to </p> <p> take your injection.</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-668414682"></a><img alt="fig-f" src="/dailymed/image.cfm?name=image-15.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Step 2. Check the Saxenda flow with each new pen.</span> </p> <dl> <dt>•</dt> <dd>Check the Saxenda flow<span class="Bold"> before your first injection with each new pen. </span> <br/>If your Saxenda pen is already in use, go to Step 3 “Select your dose”.</dd> <dt>•</dt> <dd>Turn the dose selector<span class="Bold"> until the dose counter shows the flow check symbol (</span><a name="id-1775475502"></a><img alt="flow-check" src="/dailymed/image.cfm?name=image-16.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/><span class="Bold">).</span> </dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id323787788"></a><img alt="fig-g" src="/dailymed/image.cfm?name=image-17.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd>Hold the pen with the needle pointing up. <br/> <span class="Bold">Press and hold in the dose button</span> until the dose counter shows 0. The 0 must line up with the dose pointer. <br/>A drop of Saxenda will appear at the needle tip.</dd> <dt>•</dt> <dd> <span class="Bold">If no drop appears,</span> repeat Step 2 above as shown in Figures <span class="Bold">G</span> and <span class="Bold">H</span> up to 6 times. If there is still no drop, change the needle and repeat Step 2 as shown in Figures <span class="Bold">G</span> and <span class="Bold">H</span> 1 more time. <br/> <span class="Bold">Do not use the pen </span>if a drop of Saxenda still does not appear<span class="Bold">. </span>Contact Novo Nordisk at 1-844-363-4448.</dd> </dl> <p class="First"> <a name="id-474689704"></a><img alt="note " src="/dailymed/image.cfm?name=image-18.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/><span class="Bold">Always make sure that a drop appears </span>at the needle tip before you use a new pen for the first time. This makes sure that Saxenda flows. <br/>If no drop appears, you will <span class="Bold">not</span> inject any Saxenda, even though the dose counter may move. <span class="Bold">This may mean that there is a blocked or damaged needle. </span> </p> <p> <a name="id-1037273879"></a><img alt="info" src="/dailymed/image.cfm?name=image-19.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/>A small drop may remain at the needle tip, but it will not be injected. <br/> <span class="Bold">Only check the Saxenda flow before your first injection with each new pen.</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id1981116857"></a><img alt="fig-h" src="/dailymed/image.cfm?name=image-20.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Step 3. Select your dose</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Turn the dose selector until the dose counter shows your dose (0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg). </span> <br/>Make sure you know the dose of Saxenda you should use.</dd> <dt> </dt> <dd>If you select the wrong dose, you can turn the dose selector forward or backwards to the correct dose.</dd> </dl> <p> <a name="id508038600"></a><img alt="note " src="/dailymed/image.cfm?name=image-21.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/><span class="Bold">Always use the dose counter and the dose pointer to see how</span> </p> <p> <span class="Bold"> many mg you select. </span> </p> <p> You will hear a “click” every time you turn the dose selector. <span class="Bold">Do </span> </p> <p> <span class="Bold"> not set the dose by counting the number of clicks you hear.</span> <br/> Do not use the pen scale to set the dose. It does not show exactly </p> <p> how much Saxenda is left in your pen.<br/> <span class="Bold"> Only doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg can be </span> </p> <p> <span class="Bold"> selected with the dose selector.</span> The selected dose must line up </p> <p> exactly with the dose pointer to make sure that you get a correct</p> <p> dose.</p> <p> <a name="id-106666247"></a><img alt="info" src="/dailymed/image.cfm?name=image-22.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/>The dose selector changes the dose. Only the dose counter and dose </p> <p> pointer will show how many mg you select for each dose. </p> <p> <br/> You can select up to 3 mg each dose. When your pen contains less </p> <p> than 3 mg the dose counter stops before 3 mg is shown.<br/> The dose selector clicks differently when turned forward, </p> <p> backwards or past the number of mg left. Do not count the pen </p> <p> clicks.</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-961886394"></a><img alt="fig-i" src="/dailymed/image.cfm?name=image-23.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <a name="id632139588"></a><img alt="info" src="/dailymed/image.cfm?name=image-24.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/><span class="Bold">How much Saxenda is left?</span> </p> <dl> <dt>•</dt> <dd>The <span class="Bold">pen scale</span> shows you about how much Saxenda is left in your pen.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id731128707"></a><img alt="fig-j" src="/dailymed/image.cfm?name=image-25.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">To see how much Saxenda is left, </span>use the dose counter<span class="Bold">: </span> <br/>Turn the dose selector until the <span class="Bold">dose counter</span> stops. <br/>If it shows 3, <span class="Bold">at least 3 mg</span> are left in your pen. If the <span class="Bold">dose counter stops before 3 mg,</span> there is not enough Saxenda left for a full dose of 3 mg.</dd> </dl> <p class="First"> <a name="id-1177262717"></a><img alt="info" src="/dailymed/image.cfm?name=image-26.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/><span class="Bold"> If you need more Saxenda than what is left in your pen </span> <br/>Only if trained or told by your healthcare provider, you may split your dose between your current pen and a new pen. Use a calculator to plan the doses as instructed by your healthcare provider.</p> <p> <a name="id-1257045057"></a><img alt="note " src="/dailymed/image.cfm?name=image-27.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/><span class="Bold">Be very careful to calculate correctly. </span> <br/>If you are not sure how to split your dose using 2 pens, then select and inject the dose you need with a new pen.</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-237939120"></a><img alt="fig-k" src="/dailymed/image.cfm?name=image-28.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Step 4. Inject your dose</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Insert the needle into your skin </span>as your healthcare provider has shown you.</dd> <dt>•</dt> <dd> <span class="Bold">Make sure you can see the dose counter. </span>Do not cover it with your fingers. This could stop the injection.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-2054693829"></a><img alt="fig-l" src="/dailymed/image.cfm?name=image-29.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Press and hold down the dose button until the dose counter shows 0. </span>The 0 must line up with the dose pointer. You may then hear or feel a click.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id817236678"></a><img alt="fig-m" src="/dailymed/image.cfm?name=image-30.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Keep the needle in your skin after</span> the dose counter has returned to 0 and<span class="Bold"> count slowly to 6. </span> </dd> <dt>•</dt> <dd>If the needle is removed earlier, you may see a stream of Saxenda coming from the needle tip. If this happens, the full dose will not be delivered.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-1650124496"></a><img alt="fig-n" src="/dailymed/image.cfm?name=image-31.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Remove the needle from your skin. </span> <br/>If blood appears at the injection site, press lightly. Do not rub the area.</dd> </dl> <p class="First"> <a name="id-2090841362"></a><img alt="note " src="/dailymed/image.cfm?name=image-32.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/><span class="Bold">Always watch the dose counter to know how many mg you</span> </p> <p> <span class="Bold"> inject.</span> Hold the dose button down until the dose counter shows 0.</p> <dl> <dt> </dt> <dd> <span class="Bold"> How to identify a blocked or damaged needle?</span> </dd> </dl> <dl> <dt> </dt> <dd> <dl> <dt>•</dt> <dd>If 0 does not appear in the dose counter after continuously pressing the dose button, you may have used a blocked or damaged needle.</dd> <dt>•</dt> <dd>If this happens you have <span class="Bold">not</span> received <span class="Bold">any</span> Saxenda even though the dose counter has moved from the original dose that you have set.</dd> </dl> </dd> <dt> </dt> <dd> <span class="Bold"> How to handle a blocked needle?</span> </dd> <dt> </dt> <dd> Change the needle as described in Step 5, and repeat all steps </dd> <dt> </dt> <dd> starting with Step 1: <span class="Bold">“Prepare your pen with a new needle”</span>. </dd> <dt> </dt> <dd> Make sure you select the full dose you need. </dd> <dt> </dt> <dd> <span class="Bold"> Never touch the dose counter when you inject. </span>This can stop the </dd> <dt> </dt> <dd> injection.</dd> </dl> <p> <a name="id-534427408"></a><img alt="info" src="/dailymed/image.cfm?name=image-33.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/>You may see a drop of Saxenda at the needle tip after injecting. This</p> <p> is normal and does not affect your dose.</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-2065622938"></a><img alt="fog-o" src="/dailymed/image.cfm?name=image-34.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Step 5. After your injection</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Carefully remove the needle from the pen.</span> Do not put the needle caps back on the needle, to avoid needle sticks.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id1549719524"></a><img alt="fig-p" src="/dailymed/image.cfm?name=image-35.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Place the needle in a sharps container </span>right away to reduce the risk of needle sticks.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-1269240922"></a><img alt="fig-q" src="/dailymed/image.cfm?name=image-36.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Put the pen cap on </span>your pen after each use to protect Saxenda from light.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-1108191968"></a><img alt="fig-r" src="/dailymed/image.cfm?name=image-37.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <a name="id-176197219"></a><img alt="info" src="/dailymed/image.cfm?name=image-38.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/> If you do not have a sharps container, follow a 1-handed needle </p> <p> recapping method. Carefully slip the needle into the outer needle </p> <p> cap. Dispose of the needle in a sharps container as soon as possible.</p> <p> <a name="id-387724360"></a><img alt="note " src="/dailymed/image.cfm?name=image-39.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/><span class="Bold">Never try to put the inner needle cap back on the needle. </span>You </p> <p> may stick yourself with the needle.<br/> <span class="Bold"> Always remove the needle from your pen. </span> <br/> This prevents contamination, infection, leakage of Saxenda, and </p> <p> blocked needles leading to the wrong dose. If the needle is </p> <p> blocked, you will <span class="Bold">not</span> inject any Saxenda.</p> <p> <a name="id-1113599147"></a><img alt="info" src="/dailymed/image.cfm?name=image-40.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/><span class="Bold">Always dispose of the needle after each injection</span>. </p> <dl> <dt>•</dt> <dd> <span class="Bold">Do not throw away in the household trash. </span>Put the needle and any empty Saxenda pen or any pen used for 30 days still containing Saxenda in a FDA-cleared sharps disposal container right away after use.</dd> <dt>•</dt> <dd>If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:<dl> <dt>o</dt> <dd>made of a heavy-duty plastic</dd> <dt>o</dt> <dd>can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out upright and stable during use</dd> <dt>o</dt> <dd>leak-resistant</dd> <dt>o</dt> <dd>properly labeled to warn of hazardous waste inside the container</dd> </dl> </dd> <dt>•</dt> <dd>When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about the safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: <a href="http://www.fda.gov/safesharpsdisposal">http://www.fda.gov/safesharpsdisposal</a> </dd> <dt>•</dt> <dd>Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.</dd> <dt>•</dt> <dd>Safely dispose of Saxenda that is out of date or no longer needed.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule" valign="top"><a name="id-1156066947"></a><img alt="fig-s" src="/dailymed/image.cfm?name=image-41.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <a name="id453993917"></a><img alt="note " src="/dailymed/image.cfm?name=image-42.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143"/><span class="Bold"> Important</span> </p> <dl> <dt>•</dt> <dd>Caregivers must <span class="Bold">be very careful when handling used needles</span> to prevent needle sticks and cross infection.</dd> <dt>•</dt> <dd>Never use a syringe to withdraw Saxenda from your pen.</dd> <dt>•</dt> <dd>Always carry an extra pen and new needles with you, in case of loss or damage.</dd> <dt>•</dt> <dd>Always keep your pen and needles<span class="Bold"> out of reach of others, </span>especially children.</dd> <dt>•</dt> <dd> <span class="Bold">Do not share your Saxenda pen or needles with anyone else.</span> You may give an infection to them or get an infection from them.</dd> <dt>•</dt> <dd> <span class="Bold">Always keep your pen with you.</span> Do not leave it in a car or other place where it can get too hot or too cold.</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Caring for your pen</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Do not drop your pen or</span> knock it against hard surfaces. If you drop it or suspect a problem, attach a new needle and check the Saxenda flow before you inject.</dd> <dt>•</dt> <dd> <span class="Bold">Do not try to repair your pen </span>or pull it apart.</dd> <dt>•</dt> <dd> <span class="Bold">Do not expose your pen to dust, dirt or liquid. </span> </dd> <dt>•</dt> <dd> <span class="Bold">Do not wash, soak, or lubricate your pen. </span>If necessary, clean it with mild detergent on a moistened cloth.</dd> </dl> <p> <span class="Bold">How should I store my Saxenda pen?</span> </p> <dl> <dt>•</dt> <dd>Store your <span class="Bold">new, unused</span> Saxenda pens in the refrigerator at 36°F to 46°F (2°C to 8°C).</dd> <dt>•</dt> <dd> <span class="Bold">Store your pen in use</span> for 30 days at 59ºF to 86ºF (15ºC to 30ºC) or in a refrigerator at 36°F to 46°F (2°C to 8°C).</dd> <dt>•</dt> <dd>The Saxenda pen you are using should be thrown away after 30 days, even if it still has Saxenda left in it.</dd> <dt>•</dt> <dd> <span class="Bold">Do not</span> freeze Saxenda. <span class="Bold">Do not</span> use Saxenda if it has been frozen.</dd> <dt>•</dt> <dd>Unused Saxenda pens may be used until the expiration date printed on the label, if kept in the refrigerator.</dd> <dt>•</dt> <dd>Keep Saxenda away from heat and out of the light.</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"109.7%\">\n<col width=\"55%\"/>\n<col width=\"45%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Step 1. Prepare your pen with a new needle</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Wash your hands </span>with soap and water.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Check the name and colored label </span>of your pen, to make sure that it contains Saxenda. This is especially important if you take more than 1 type of medicine.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Pull off the pen cap.</span>\n</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id1293942579\"></a><img alt=\"fig-a\" src=\"/dailymed/image.cfm?name=image-05.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Check that Saxenda in your pen is clear</span> and colorless. <br/>Look through the pen window. If Saxenda looks cloudy, do not use the pen.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-1158379815\"></a><img alt=\"fig-b\" src=\"/dailymed/image.cfm?name=image-06.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Take a new needle,</span> and tear off the paper tab.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-1889567842\"></a><img alt=\"fig-c\" src=\"/dailymed/image.cfm?name=image-07.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Push the needle straight onto the pen. Turn until it is on tight.</span>\n</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-1391882563\"></a><img alt=\"fig-d\" src=\"/dailymed/image.cfm?name=image-08.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Pull off the outer needle cap.</span> Do not throw it away.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id878668504\"></a><img alt=\"fig-e\" src=\"/dailymed/image.cfm?name=image-11.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Pull off the inner needle cap </span>and throw it away. <br/>A drop of Saxenda may appear at the needle tip. This is normal, but you must still check the Saxenda flow, if you use a new pen for the first time. </dd>\n</dl>\n<p class=\"First\">\n<a name=\"id1253545431\"></a><img alt=\"note \" src=\"/dailymed/image.cfm?name=image-13.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/><span class=\"Bold\">Always use a new needle for each injection.</span>\n</p>\n<p> This will prevent contamination, infection, leakage of Saxenda,</p>\n<p> and blocked needles leading to the wrong dose. <br/>\n<span class=\"Bold\"> Never use a bent or damaged needle.</span>\n</p>\n<p>\n<a name=\"id-1321036061\"></a><img alt=\"info\" src=\"/dailymed/image.cfm?name=image-14.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/><span class=\"Bold\"> Do not attach a new needle</span> to your pen until you are ready to </p>\n<p> take your injection.</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-668414682\"></a><img alt=\"fig-f\" src=\"/dailymed/image.cfm?name=image-15.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Step 2. Check the Saxenda flow with each new pen.</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Check the Saxenda flow<span class=\"Bold\"> before your first injection with each new pen. </span>\n<br/>If your Saxenda pen is already in use, go to Step 3 “Select your dose”.</dd>\n<dt>•</dt>\n<dd>Turn the dose selector<span class=\"Bold\"> until the dose counter shows the flow check symbol (</span><a name=\"id-1775475502\"></a><img alt=\"flow-check\" src=\"/dailymed/image.cfm?name=image-16.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/><span class=\"Bold\">).</span>\n</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id323787788\"></a><img alt=\"fig-g\" src=\"/dailymed/image.cfm?name=image-17.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>Hold the pen with the needle pointing up. <br/>\n<span class=\"Bold\">Press and hold in the dose button</span> until the dose counter shows 0. The 0 must line up with the dose pointer. <br/>A drop of Saxenda will appear at the needle tip.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">If no drop appears,</span> repeat Step 2 above as shown in Figures <span class=\"Bold\">G</span> and <span class=\"Bold\">H</span> up to 6 times. If there is still no drop, change the needle and repeat Step 2 as shown in Figures <span class=\"Bold\">G</span> and <span class=\"Bold\">H</span> 1 more time. <br/>\n<span class=\"Bold\">Do not use the pen </span>if a drop of Saxenda still does not appear<span class=\"Bold\">. </span>Contact Novo Nordisk at 1-844-363-4448.</dd>\n</dl>\n<p class=\"First\">\n<a name=\"id-474689704\"></a><img alt=\"note \" src=\"/dailymed/image.cfm?name=image-18.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/><span class=\"Bold\">Always make sure that a drop appears </span>at the needle tip before you use a new pen for the first time. This makes sure that Saxenda flows. <br/>If no drop appears, you will <span class=\"Bold\">not</span> inject any Saxenda, even though the dose counter may move. <span class=\"Bold\">This may mean that there is a blocked or damaged needle. </span>\n</p>\n<p>\n<a name=\"id-1037273879\"></a><img alt=\"info\" src=\"/dailymed/image.cfm?name=image-19.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/>A small drop may remain at the needle tip, but it will not be injected. <br/>\n<span class=\"Bold\">Only check the Saxenda flow before your first injection with each new pen.</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id1981116857\"></a><img alt=\"fig-h\" src=\"/dailymed/image.cfm?name=image-20.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Step 3. Select your dose</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Turn the dose selector until the dose counter shows your dose (0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg). </span>\n<br/>Make sure you know the dose of Saxenda you should use.</dd>\n<dt> </dt>\n<dd>If you select the wrong dose, you can turn the dose selector forward or backwards to the correct dose.</dd>\n</dl>\n<p>\n<a name=\"id508038600\"></a><img alt=\"note \" src=\"/dailymed/image.cfm?name=image-21.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/><span class=\"Bold\">Always use the dose counter and the dose pointer to see how</span>\n</p>\n<p>\n<span class=\"Bold\"> many mg you select. </span>\n</p>\n<p> You will hear a “click” every time you turn the dose selector. <span class=\"Bold\">Do </span>\n</p>\n<p>\n<span class=\"Bold\"> not set the dose by counting the number of clicks you hear.</span>\n<br/> Do not use the pen scale to set the dose. It does not show exactly </p>\n<p> how much Saxenda is left in your pen.<br/>\n<span class=\"Bold\"> Only doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg can be </span>\n</p>\n<p>\n<span class=\"Bold\"> selected with the dose selector.</span> The selected dose must line up </p>\n<p> exactly with the dose pointer to make sure that you get a correct</p>\n<p> dose.</p>\n<p>\n<a name=\"id-106666247\"></a><img alt=\"info\" src=\"/dailymed/image.cfm?name=image-22.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/>The dose selector changes the dose. Only the dose counter and dose </p>\n<p> pointer will show how many mg you select for each dose. </p>\n<p>\n<br/> You can select up to 3 mg each dose. When your pen contains less </p>\n<p> than 3 mg the dose counter stops before 3 mg is shown.<br/> The dose selector clicks differently when turned forward, </p>\n<p> backwards or past the number of mg left. Do not count the pen </p>\n<p> clicks.</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-961886394\"></a><img alt=\"fig-i\" src=\"/dailymed/image.cfm?name=image-23.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<a name=\"id632139588\"></a><img alt=\"info\" src=\"/dailymed/image.cfm?name=image-24.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/><span class=\"Bold\">How much Saxenda is left?</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>The <span class=\"Bold\">pen scale</span> shows you about how much Saxenda is left in your pen.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id731128707\"></a><img alt=\"fig-j\" src=\"/dailymed/image.cfm?name=image-25.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">To see how much Saxenda is left, </span>use the dose counter<span class=\"Bold\">: </span>\n<br/>Turn the dose selector until the <span class=\"Bold\">dose counter</span> stops. <br/>If it shows 3, <span class=\"Bold\">at least 3 mg</span> are left in your pen. If the <span class=\"Bold\">dose counter stops before 3 mg,</span> there is not enough Saxenda left for a full dose of 3 mg.</dd>\n</dl>\n<p class=\"First\">\n<a name=\"id-1177262717\"></a><img alt=\"info\" src=\"/dailymed/image.cfm?name=image-26.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/><span class=\"Bold\"> If you need more Saxenda than what is left in your pen </span>\n<br/>Only if trained or told by your healthcare provider, you may split your dose between your current pen and a new pen. Use a calculator to plan the doses as instructed by your healthcare provider.</p>\n<p>\n<a name=\"id-1257045057\"></a><img alt=\"note \" src=\"/dailymed/image.cfm?name=image-27.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/><span class=\"Bold\">Be very careful to calculate correctly. </span>\n<br/>If you are not sure how to split your dose using 2 pens, then select and inject the dose you need with a new pen.</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-237939120\"></a><img alt=\"fig-k\" src=\"/dailymed/image.cfm?name=image-28.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Step 4. Inject your dose</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Insert the needle into your skin </span>as your healthcare provider has shown you.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Make sure you can see the dose counter. </span>Do not cover it with your fingers. This could stop the injection.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-2054693829\"></a><img alt=\"fig-l\" src=\"/dailymed/image.cfm?name=image-29.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Press and hold down the dose button until the dose counter shows 0. </span>The 0 must line up with the dose pointer. You may then hear or feel a click.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id817236678\"></a><img alt=\"fig-m\" src=\"/dailymed/image.cfm?name=image-30.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Keep the needle in your skin after</span> the dose counter has returned to 0 and<span class=\"Bold\"> count slowly to 6. </span>\n</dd>\n<dt>•</dt>\n<dd>If the needle is removed earlier, you may see a stream of Saxenda coming from the needle tip. If this happens, the full dose will not be delivered.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-1650124496\"></a><img alt=\"fig-n\" src=\"/dailymed/image.cfm?name=image-31.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Remove the needle from your skin. </span>\n<br/>If blood appears at the injection site, press lightly. Do not rub the area.</dd>\n</dl>\n<p class=\"First\">\n<a name=\"id-2090841362\"></a><img alt=\"note \" src=\"/dailymed/image.cfm?name=image-32.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/><span class=\"Bold\">Always watch the dose counter to know how many mg you</span>\n</p>\n<p>\n<span class=\"Bold\"> inject.</span> Hold the dose button down until the dose counter shows 0.</p>\n<dl>\n<dt> </dt>\n<dd>\n<span class=\"Bold\"> How to identify a blocked or damaged needle?</span>\n</dd>\n</dl>\n<dl>\n<dt> </dt>\n<dd>\n<dl>\n<dt>•</dt>\n<dd>If 0 does not appear in the dose counter after continuously pressing the dose button, you may have used a blocked or damaged needle.</dd>\n<dt>•</dt>\n<dd>If this happens you have <span class=\"Bold\">not</span> received <span class=\"Bold\">any</span> Saxenda even though the dose counter has moved from the original dose that you have set.</dd>\n</dl>\n</dd>\n<dt> </dt>\n<dd>\n<span class=\"Bold\"> How to handle a blocked needle?</span>\n</dd>\n<dt> </dt>\n<dd> Change the needle as described in Step 5, and repeat all steps </dd>\n<dt> </dt>\n<dd> starting with Step 1: <span class=\"Bold\">“Prepare your pen with a new needle”</span>. </dd>\n<dt> </dt>\n<dd> Make sure you select the full dose you need. </dd>\n<dt> </dt>\n<dd>\n<span class=\"Bold\"> Never touch the dose counter when you inject. </span>This can stop the </dd>\n<dt> </dt>\n<dd> injection.</dd>\n</dl>\n<p>\n<a name=\"id-534427408\"></a><img alt=\"info\" src=\"/dailymed/image.cfm?name=image-33.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/>You may see a drop of Saxenda at the needle tip after injecting. This</p>\n<p> is normal and does not affect your dose.</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-2065622938\"></a><img alt=\"fog-o\" src=\"/dailymed/image.cfm?name=image-34.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Step 5. After your injection</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Carefully remove the needle from the pen.</span> Do not put the needle caps back on the needle, to avoid needle sticks.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id1549719524\"></a><img alt=\"fig-p\" src=\"/dailymed/image.cfm?name=image-35.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Place the needle in a sharps container </span>right away to reduce the risk of needle sticks.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-1269240922\"></a><img alt=\"fig-q\" src=\"/dailymed/image.cfm?name=image-36.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Put the pen cap on </span>your pen after each use to protect Saxenda from light.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-1108191968\"></a><img alt=\"fig-r\" src=\"/dailymed/image.cfm?name=image-37.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<a name=\"id-176197219\"></a><img alt=\"info\" src=\"/dailymed/image.cfm?name=image-38.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/> If you do not have a sharps container, follow a 1-handed needle </p>\n<p> recapping method. Carefully slip the needle into the outer needle </p>\n<p> cap. Dispose of the needle in a sharps container as soon as possible.</p>\n<p>\n<a name=\"id-387724360\"></a><img alt=\"note \" src=\"/dailymed/image.cfm?name=image-39.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/><span class=\"Bold\">Never try to put the inner needle cap back on the needle. </span>You </p>\n<p> may stick yourself with the needle.<br/>\n<span class=\"Bold\"> Always remove the needle from your pen. </span>\n<br/> This prevents contamination, infection, leakage of Saxenda, and </p>\n<p> blocked needles leading to the wrong dose. If the needle is </p>\n<p> blocked, you will <span class=\"Bold\">not</span> inject any Saxenda.</p>\n<p>\n<a name=\"id-1113599147\"></a><img alt=\"info\" src=\"/dailymed/image.cfm?name=image-40.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/><span class=\"Bold\">Always dispose of the needle after each injection</span>. </p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not throw away in the household trash. </span>Put the needle and any empty Saxenda pen or any pen used for 30 days still containing Saxenda in a FDA-cleared sharps disposal container right away after use.</dd>\n<dt>•</dt>\n<dd>If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:<dl>\n<dt>o</dt>\n<dd>made of a heavy-duty plastic</dd>\n<dt>o</dt>\n<dd>can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out upright and stable during use</dd>\n<dt>o</dt>\n<dd>leak-resistant</dd>\n<dt>o</dt>\n<dd>properly labeled to warn of hazardous waste inside the container</dd>\n</dl>\n</dd>\n<dt>•</dt>\n<dd>When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about the safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: <a href=\"http://www.fda.gov/safesharpsdisposal\">http://www.fda.gov/safesharpsdisposal</a>\n</dd>\n<dt>•</dt>\n<dd>Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.</dd>\n<dt>•</dt>\n<dd>Safely dispose of Saxenda that is out of date or no longer needed.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\"><a name=\"id-1156066947\"></a><img alt=\"fig-s\" src=\"/dailymed/image.cfm?name=image-41.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<a name=\"id453993917\"></a><img alt=\"note \" src=\"/dailymed/image.cfm?name=image-42.jpg&amp;setid=3946d389-0926-4f77-a708-0acb8153b143\"/><span class=\"Bold\"> Important</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Caregivers must <span class=\"Bold\">be very careful when handling used needles</span> to prevent needle sticks and cross infection.</dd>\n<dt>•</dt>\n<dd>Never use a syringe to withdraw Saxenda from your pen.</dd>\n<dt>•</dt>\n<dd>Always carry an extra pen and new needles with you, in case of loss or damage.</dd>\n<dt>•</dt>\n<dd>Always keep your pen and needles<span class=\"Bold\"> out of reach of others, </span>especially children.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not share your Saxenda pen or needles with anyone else.</span> You may give an infection to them or get an infection from them.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Always keep your pen with you.</span> Do not leave it in a car or other place where it can get too hot or too cold.</dd>\n</dl>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Caring for your pen</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not drop your pen or</span> knock it against hard surfaces. If you drop it or suspect a problem, attach a new needle and check the Saxenda flow before you inject.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not try to repair your pen </span>or pull it apart.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not expose your pen to dust, dirt or liquid. </span>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not wash, soak, or lubricate your pen. </span>If necessary, clean it with mild detergent on a moistened cloth.</dd>\n</dl>\n<p>\n<span class=\"Bold\">How should I store my Saxenda pen?</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Store your <span class=\"Bold\">new, unused</span> Saxenda pens in the refrigerator at 36°F to 46°F (2°C to 8°C).</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Store your pen in use</span> for 30 days at 59ºF to 86ºF (15ºC to 30ºC) or in a refrigerator at 36°F to 46°F (2°C to 8°C).</dd>\n<dt>•</dt>\n<dd>The Saxenda pen you are using should be thrown away after 30 days, even if it still has Saxenda left in it.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not</span> freeze Saxenda. <span class=\"Bold\">Do not</span> use Saxenda if it has been frozen.</dd>\n<dt>•</dt>\n<dd>Unused Saxenda pens may be used until the expiration date printed on the label, if kept in the refrigerator.</dd>\n<dt>•</dt>\n<dd>Keep Saxenda away from heat and out of the light.</dd>\n</dl>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td>\n</tr>\n</tbody>\n</table></div>" }

This Medication Guide and Instructions for Use have been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "\nThis Medication Guide and Instructions for Use have been approved by the U.S. Food and Drug Administration.\n" }

December 2020

{ "type": "p", "children": [], "text": "December 2020" }

NDC 0169-2800-15

{ "type": "p", "children": [], "text": "NDC 0169-2800-15" }

List 280015

{ "type": "p", "children": [], "text": "List 280015" }

Saxenda ®

{ "type": "p", "children": [], "text": "Saxenda ®\n" }

(liraglutide) injection

{ "type": "p", "children": [], "text": "(liraglutide) injection" }

18 mg/3 mL (6 mg/mL)

{ "type": "p", "children": [], "text": "\n18 mg/3 mL (6 mg/mL)\n" }

5×3 mL Prefilled Pens

{ "type": "p", "children": [], "text": "5×3 mL Prefilled Pens " }

For subcutaneous use only

{ "type": "p", "children": [], "text": "\nFor subcutaneous use only\n" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n" }

Single Patient Use Only

{ "type": "p", "children": [], "text": "\nSingle Patient Use Only\n" }

Discard pen 30 days after first use

{ "type": "p", "children": [], "text": "Discard pen 30 days after first use " }

Recommended for use with NovoFine® or NovoTwist® disposable needles.

{ "type": "p", "children": [], "text": "\nRecommended for use with NovoFine® or NovoTwist® disposable needles.\n" }

REFRIGERATE – DO NOT FREEZE

{ "type": "p", "children": [], "text": "\nREFRIGERATE – DO NOT FREEZE\n" }

Protect from light.

{ "type": "p", "children": [], "text": "\nProtect from light.\n" }

Dispense the enclosed Medication Guide to each patient

{ "type": "p", "children": [], "text": "Dispense the enclosed Medication Guide to each patient" }