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 C 172 H 265 N 43 O 51 and the molecular weight is 3751.2 Daltons. The structural formula ( Figure 1 ) is: Figure 1. Structural Formula of liraglutide 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). structural-formula

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: • Adults and pediatric patients aged 12 years and older with body weight greater than 60 kg and obesity. • Adults with overweight in the presence of at least one weight-related comorbid condition. Limitations of Use • SAXENDA contains liraglutide. Coadministration with other liraglutide-containing products or with any other glucagon-like peptide-1 (GLP-1) receptor agonist is not recommended. • The safety and effectiveness of SAXENDA in pediatric patients with type 2 diabetes have not been established. SAXENDA is a glucagon like peptide 1 (GLP-1) receptor agonist indicated in combination with a reduced calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in: • Adults and pediatric patients aged 12 years and older with body weight greater than 60 kg and obesity. • Adults with overweight in the presence of at least one weight-related comorbid condition. Limitations of Use: • Coadministration with other liraglutide-containing products or with any other GLP-1 receptor agonist is not recommended. • The safety and effectiveness of SAXENDA in pediatric patients with type 2 diabetes have not been established.

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. Injection: 6 mg/mL 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.

• Inject SAXENDA subcutaneously in the abdomen, thigh, or upper arm once daily at any time of day, without regard to the timing of meals. • The recommended dose of SAXENDA is 3 mg daily. • Initiate at 0.6 mg per day for one week. In weekly intervals, increase the dose until a dose of 3 mg is reached. • If pediatric patients do not tolerate an increased dose during dose escalation, the dose may also be lowered to the previous level. Dose escalation for pediatric patients may take up to 8 weeks. • Pediatric patients who do not tolerate 3 mg daily may have their dose reduced to 2.4 mg daily. • Adult patients with type 2 diabetes should monitor blood glucose prior to starting SAXENDA and during SAXENDA treatment

Important Administration Instructions • Prior to initiation of SAXENDA, train patients on proper injection technique. Refer to the accompanying Instructions for Use for complete administration instructions with illustrations. • Inspect SAXENDA visually prior to each injection. Only use if solution is clear, colorless, and contains no particles. • Administer SAXENDA in combination with a reduced-calorie diet and increased physical activity. • Inject SAXENDA subcutaneously once daily at any time of day, without regard to the timing of meals. • Inject SAXENDA subcutaneously in the abdomen, thigh, or upper arm. No dosage adjustment is needed if changing the injection site and/or timing. • Rotate injection sites within the same region in order to reduce the risk of cutaneous amyloidosis . • If a dose is missed, resume the once-daily regimen as prescribed with the next scheduled dose. Do not administer an extra dose or increase the dose to make up for the missed dose. • If more than 3 days have elapsed since the last SAXENDA dosage, reinitiate SAXENDA at 0.6 mg daily and follow the dosage escalation schedule in Table 1 , to reduce the risk of gastrointestinal adverse reactions associated with reinitiation of treatment

Dosage in Adults and Pediatric Patients Aged 12 Years and Older • Initiate SAXENDA with a dose of 0.6 mg daily for one week. Then follow the dosage escalation schedule in Table 1 to reduce the risk of gastrointestinal adverse reactions . Table 1. Dosage Escalation Schedule Week Daily Dose 1 0.6 mg 2 1.2 mg 3 1.8 mg 4 2.4 mg 5 and onward 3 mg Adult Patients • For adults, the recommended dosage of SAXENDA is 3 mg daily, lower dosages are for titration only. • Discontinue SAXENDA if the patient cannot tolerate the 3 mg dosage. • If patients do not tolerate an increased dose during dosage escalation, consider delaying dosage escalation for approximately one additional week. • Evaluate the change in body weight 16 weeks after initiating SAXENDA and discontinue SAXENDA if the patient has not lost at least 4% of baseline body weight, since it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment. • In adult patients with type 2 diabetes, monitor blood glucose prior to starting SAXENDA and during SAXENDA treatment. Pediatric Patients • For pediatric patients, the recommended maintenance dosage of SAXENDA is 3 mg daily. Pediatric patients who do not tolerate 3 mg daily may have their maintenance dose reduced to 2.4 mg daily. Discontinue SAXENDA if the patient cannot tolerate the 2.4 mg dose. • If pediatric patients do not tolerate an increased dose during dosage escalation, the dose may also be lowered to the previous level. Dosage escalation for pediatric patients may take up to 8 weeks. • Evaluate the change in BMI after 12 weeks on the maintenance dose and discontinue SAXENDA if the patient has not had a reduction in BMI of at least 1% from baseline, since it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment.

• Acute Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, including SAXENDA. Discontinue if pancreatitis is suspected. • Acute Gallbladder Disease: If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated. • Hypoglycemia: Can occur in adults when SAXENDA is used with an insulin secretagogue (e.g. a sulfonylurea) or insulin. The risk may be lowered by a reduction in the dose of concomitantly administered insulin secretagogues or insulin. In the pediatric clinical trial, patients did not have type 2 diabetes. Hypoglycemia occurred in SAXENDA-treated pediatric patients. Inform all patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia. • Heart Rate Increase: Monitor heart rate at regular intervals. • Acute Kidney Injury Due to Volume Depletion: Monitor renal function in patients reporting adverse reactions that could lead to volume depletion. • Severe Gastrointestinal Adverse Reactions: Use has been associated with gastrointestinal adverse reactions, sometimes severe. SAXENDA is not recommended in patients with severe gastroparesis. • Hypersensitivity Reactions: Postmarketing reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema). Discontinue SAXENDA and other suspect medications and promptly seek medical advice. • Pulmonary Aspiration During General Anesthesia or Deep Sedation: Has been reported in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures. Instruct patients to inform healthcare providers of any planned surgeries or procedures. 5.1 Risk of Thyroid C-cell Tumors 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 . 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 Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including liraglutide . After initiation of SAXENDA, observe patients carefully for signs and symptoms of acute pancreatitis which may include persistent or severe abdominal pain (sometimes radiating to the back) and which may or may not be accompanied by nausea or vomiting. If pancreatitis is suspected, discontinue SAXENDA and initiate appropriate management

Acute Gallbladder Disease 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

Hypoglycemia 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 . 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 . Inform all pediatric patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia

Heart Rate Increase 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

Acute Kidney Injury Due to Volume Depletion There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with liraglutide . The majority of the reported events occurred in patients who had experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea . Monitor renal function in patients reporting adverse reactions to SAXENDA that could lead to volume depletion, especially during dosage initiation and escalation

Severe Gastrointestinal Adverse Reactions Use of GLP-1 receptor agonists, including liraglutide, has been associated with gastrointestinal adverse reactions, sometimes severe . In SAXENDA clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving SAXENDA (4.8%) than placebo (1.4%). Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists. SAXENDA is not recommended in patients with severe gastroparesis

Hypersensitivity Reactions There have been reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema) in patients treated with SAXENDA . 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

Pulmonary Aspiration During General Anesthesia or Deep Sedation SAXENDA delays gastric emptying . 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.

SAXENDA delays gastric emptying. May impact absorption of concomitantly administered oral medications. Use with caution

Oral Medications 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.