Saxenda

Indications and Usage ( 1 )...................................................05/2025 Dosage and Administration, Patient Selection ( 2.1 ).......(Removed) 05/2025 Contraindications, Pregnancy ( 4 )............................(Removed) 05/2025 Warnings and Precautions, Severe Gastrointestinal Adverse Reactions ( 5.7 )....................10/2025 Suicidal Behavior and Ideation ( 5.9 )....................(Removed) 02/2026

1 INDICATIONS AND USAGE SAXENDA is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in: • Adult patients with an initial body mass index (BMI) of [see Dosage and Administration ( 2.1 )] : ▪ 30 kg/m 2 or greater (obese), or ▪ 27 kg/m 2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia) • Pediatric patients aged 12 years and older with: ▪ body weight above 60 kg and ▪ an initial BMI corresponding to 30 kg/m 2 or greater for adults (obese) by international cut-offs (Cole Criteria, Table 2) [see Dosage and Administration ( 2.1 )] Limitations of Use ▪ SAXENDA contains liraglutide and should not be coadministered with other liraglutide-containing products or with any other GLP-1 receptor agonist. ▪ The safety and effectiveness of SAXENDA in pediatric patients with type 2 diabetes have not been established. ▪ The safety and effectiveness of SAXENDA in combination with other products intended for weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations, have not been established. SAXENDA is a glucagon like peptide 1 (GLP-1) receptor agonist indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in: Adult patients with an initial body mass index (BMI) of • 30 kg/m 2 or greater (obese), or • 27 kg/m 2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g. hypertension, type 2 diabetes mellitus, or dyslipidemia) ( 1 ). Pediatric patients aged 12 years and older with: • body weight above 60 kg and • an initial BMI corresponding to 30 kg/m 2 for adults (obese) by international cut-offs ( 1 ). Limitations of Use: • SAXENDA contains liraglutide and should not be coadministered with other liraglutide-containing products or with any other GLP-1 receptor agonist ( 1 ). • The safety and effectiveness of SAXENDA in pediatric patients with type 2 diabetes have not been established ( 1 ). • The safety and efficacy of SAXENDA in combination with other products intended for weight loss have not been established ( 1) .

2 DOSAGE AND ADMINISTRATION • Inject SAXENDA subcutaneously in the abdomen, thigh, or upper arm once daily at any time of day, without regard to the timing of meals ( 2.2 ). • The recommended dose of SAXENDA is 3 mg daily ( 2.3 ). • Initiate at 0.6 mg per day for one week. In weekly intervals, increase the dose until a dose of 3 mg is reached ( 2.3 ). • 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 ( 2.3 ). • Pediatric patients who do not tolerate 3 mg daily may have their dose reduced to 2.4 mg daily ( 2.3 ). • Adult patients with type 2 diabetes should monitor blood glucose prior to starting SAXENDA and during SAXENDA treatment ( 2.3 ). 2.1 Patient Selection Select patients for SAXENDA treatment as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management based on the BMI values provided in Tables 1 and 2. Adult and Pediatric Patients BMI is calculated by dividing weight in (kilograms) by height (in meters) squared. A chart for determining BMI based on height and weight is provided in Table 1. Table 1: BMI Conversion Chart Pediatric Patients Aged 12 Years and Older BMI cut-offs for obesity in pediatric patients aged 12 years and older are presented in Table 2. Table 2: International Obesity Task Force BMI Cut-offs for Obesity by Sex and Age for Pediatric Patients Aged 12 Years and Older (Cole Criteria) Age (years) Body mass index 30 kg/m 2 Males Females 12 26.02 26.67 12.5 26.43 27.24 13 26.84 27.76 13.5 27.25 28.20 14 27.63 28.57 14.5 27.98 28.87 15 28.30 29.11 15.5 28.60 29.29 16 28.88 29.43 16.5 29.14 29.56 17 29.41 29.69 17.5 29.70 29.84 Table 2.2 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. • 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 dose 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 [see Adverse Reactions ( 6.2 )]. • 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 dose, reinitiate SAXENDA at 0.6 mg daily and follow the dose escalation schedule in Table 3, to reduce the occurrence of gastrointestinal adverse reactions associated with reinitiation of treatment. 2.3 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 dose escalation schedule in Table 3 to minimize gastrointestinal adverse reactions [see Adverse Reactions ( 6.1 )] . Table 3: Dose 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 doses are for titration only. • Discontinue SAXENDA if the patient cannot tolerate the 3 mg dose. • If patients do not tolerate an increased dose during dose escalation, consider delaying dose 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 …

3 DOSAGE FORMS AND STRENGTHS Injection: 6 mg/mL clear, colorless solution in a 3 mL pre-filled, 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 pre-filled, single-patient-use pen that delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg ( 3 ).

4 CONTRAINDICATIONS SAXENDA is contraindicated in: • Patients with a personal or family history of medullary thyroid carcinoma (MTC) or patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Warnings and Precautions ( 5.1 )]. • Patients with a serious hypersensitivity reaction to liraglutide or to any of the excipients in SAXENDA. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with SAXENDA [see Warnings and Precautions ( 5.7 )]. • Pregnancy [see Use in Specific Populations ( 8.1 )] . • Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 ( 4 , 5.1 ). • Hypersensitivity to liraglutide or any excipients in SAXENDA ( 4 , 5.7 ). • Pregnancy ( 4 , 8.1 ).

6 ADVERSE REACTIONS The following serious adverse reactions are described below or elsewhere in the prescribing information: • Risk of Thyroid C-Cell Tumors [see Warnings and Precautions ( 5.1 )] • Acute Pancreatitis [see Warnings and Precautions ( 5.2 )] • Acute Gallbladder Disease [see Warnings and Precautions ( 5.3 )] • Risk for Hypoglycemia with Concomitant Use of Anti-Diabetic Therapy [see Warnings and Precautions ( 5.4 )] • Heart Rate Increase [see Warnings and Precautions ( 5.5 )] • Acute Kidney Injury Due to Volume Depletion [see Warnings and Precautions ( 5.6 )] • Severe Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.7 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.8 )] • Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions ( 5.9 )] Most common adverse reactions, reported in greater than or equal to 5% are: nausea, diarrhea, constipation, vomiting, injection site reactions, headache, hypoglycemia, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase, upper abdominal pain, pyrexia, and gastroenteritis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc. at 1-844-363-4448 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience 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 3,384 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/m 2 , 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 . Table 2. Adverse Reactions Occurring in ≥2% of SAXENDA-treated Adult Patients and More Frequently than Placebo Placebo N=1941 % SAXENDA N=3384 % Nausea 13.8 39.3 Diarrhea 9.9 20.9 Constipation 8.5 19.4 Vomiting 3.9 15.7 Injection Site Reaction 1 10.5 13.9 Headache 12.6 13.6 Hypoglycemia in T2DM 2 6.6 12.6 Dyspepsia 2.7 9.6 Fatigue 4.6 7.5 Dizziness 5 6.9 Abdominal Pain 3.1 5.4 Increased Lipase 2.2 5.3 Upper Abdominal Pain 2.7 …

7 DRUG INTERACTIONS • SAXENDA delays gastric emptying. May impact absorption of concomitantly administered oral medications. Use with caution ( 7 ). 7.1 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.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary SAXENDA is contraindicated during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm [see Clinical Considerations] . There are no available data with liraglutide in pregnant women to inform a drug associated risk for major birth defects and miscarriage. SAXENDA should not be used during pregnancy. If a patient wishes to become pregnant, or pregnancy occurs, treatment with SAXENDA should be discontinued. 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 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryofetal risk A minimum weight gain, and no weight loss, is recommended for all pregnant women, including those who are already overweight or obese, due to the necessary 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 …

12.1 Mechanism of Action Liraglutide is an acylated human glucagon-like peptide-1 (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 1.5-2 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.

11 DESCRIPTION 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

10 OVERDOSAGE 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 Helpline (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.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied 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 5 x SAXENDA pen NDC 0169-2800-15 Recommended Storage 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.