WEGOVY

Indications and Usage ( 1 )........................................03/2024 Dosing and Administration (2.2) ............................... 07/2023 Warnings and Precautions, Hypoglycemia (5.4) ..............03/2024

1 INDICATIONS AND USAGE WEGOVY is indicated in combination with a reduced calorie diet and increased physical activity: • to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established cardiovascular disease and either obesity or overweight. • to reduce excess body weight and maintain weight reduction long term in: o Adults and pediatric patients aged 12 years and older with obesity o Adults with overweight in the presence of at least one weight-related comorbid condition. Limitations of Use • WEGOVY contains semaglutide. Coadministration with other semaglutide-containing products or with any other GLP-1 receptor agonist is not recommended. WEGOVY is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated in combination with a reduced calorie diet and increased physical activity: • to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established cardiovascular disease and either obesity or overweight (1) . • to reduce excess body weight and maintain weight reduction long term in: o Adults and pediatric patients aged 12 years and older with obesity o Adults with overweight in the presence of at least one weight-related comorbid condition (1) . Limitations of Use: • Coadministration with other semaglutide-containing products or with any other GLP-1 receptor agonist is not recommended (1).

2 DOSAGE AND ADMINISTRATION • Administer WEGOVY once weekly as an adjunct to diet and increased physical activity, on the same day each week, at any time of day, with or without meals (2.1). • Inject subcutaneously in the abdomen, thigh or upper arm (2.1). • In patients with type 2 diabetes, monitor blood glucose prior to starting and during WEGOVY treatment (2.1). • Initiate at 0.25 mg once weekly for 4 weeks. Then follow the dosage escalation schedule, titrating every 4 weeks to achieve the maintenance dosage (2.2 , 2.3). • The maintenance dosage of WEGOVY in adults is either 2.4 mg (recommended) or 1.7 mg once weekly (2.2) . • The maintenance dosage of WEGOVY in pediatric patients aged 12 years and older is 2.4 mg once weekly (2.3). 2.1 Important Monitoring and Administration Instructions • In patients with type 2 diabetes, monitor blood glucose prior to starting WEGOVY and during WEGOVY treatment [see Warnings and Precautions (5.4 )]. • Prior to initiation of WEGOVY, train patients on proper injection technique. Refer to the accompanying Instructions for Use for complete administration instructions with illustrations. • Inspect WEGOVY visually prior to each injection. Only use if solution is clear, colorless, and contains no particles. • Administer WEGOVY in combination with a reduced-calorie diet and increased physical activity. • Administer WEGOVY once weekly, on the same day each week, at any time of day, with or without meals. • Inject WEGOVY subcutaneously in the abdomen, thigh, or upper arm. The time of day and the injection site can be changed without dose adjustment. 2.2 Recommended Dosage in Adults Dosage Initiation and Escalation • Initiate WEGOVY with a dosage of 0.25 mg injected subcutaneously once weekly. Then follow the dose escalation schedule presented in Table 1 to minimize gastrointestinal adverse reactions [see Adverse Reactions ( 6.1 )] . • If patients do not tolerate a dose during dosage escalation, consider delaying dosage escalation for 4 weeks. Table 1. Recommended Dosage Regimen for Adults Treatment Weeks Once weekly Subcutaneous Dosage Initiation 1 through 4 0.25 mg Escalation 5 through 8 0.5 mg 9 through 12 1 mg 13 through 16 1.7 mg Maintenance 17 and onward 1.7 mg or 2.4 mg Maintenance Dosage • The maintenance dosage of WEGOVY in adults is either 2.4 mg (recommended) or 1.7 mg once weekly. Consider treatment response and tolerability when selecting the maintenance dosage [see Clinical Studies (14.2) ] . 2.3 Recommended Dosage in Pediatric Patients Aged 12 Years and Older Dosage Initiation and Escalation • Initiate WEGOVY according to the dosage escalation schedule in Table 2 to minimize gastrointestinal adverse reactions [see Adverse Reactions (6.1) ] . • If patients do not tolerate a dose during dosage escalation, consider delaying dosage escalation for 4 weeks. • The 0.25 mg, 0.5 mg, and 1 mg once-weekly dosages are initiation and escalation dosages and are not approved as maintenance dosages. Table 2. Recommended Dosage Regimen for Pediatric Patients Aged 12 Years and Older Treatment Weeks Once weekly Subcutaneous Dosage Initiation 1 through 4 0.25 mg a Escalation 5 through 8 0.5 mg a 9 through 12 1 mg a 13 through 16 1.7 mg b Maintenance 17 and onward 2.4 mg a Not approved as maintenance dosages b See Dosage Modifications for Adverse Reactions Maintenance Dosage • The maintenance dosage of WEGOVY in pediatric patients aged 12 years and older is 2.4 mg once weekly. Dosage Modifications for Adverse Reactions • If patients do not tolerate the 2.4 mg once weekly maintenance dosage, the maintenance dosage may be reduced to 1.7 mg once weekly. • Discontinue WEGOVY if the patient cannot tolerate the 1.7 mg once-weekly dosage. 2.4 Recommendations Regarding Missed Dose • If one dose is missed and the next scheduled dose is more than 2 days away (48 hours), administer WEGOVY as soon as possible. If one dose is missed and the next scheduled dose is less than 2 days away (48 hours), do not administer th …

3 DOSAGE FORMS AND STRENGTHS Injection: clear, colorless solution available in 5 pre-filled, disposable, single-dose pens: • 0.25 mg/0.5 mL • 0.5 mg/0.5 mL • 1 mg/0.5 mL • 1.7 mg/0.75 mL • 2.4 mg/0.75 mL Injection: pre-filled, single-dose pen that delivers doses of 0.25 mg, 0.5 mg, 1 mg, 1.7 mg or 2.4 mg ( 3 ).

4 CONTRAINDICATIONS WEGOVY is contraindicated in the following conditions: • A personal or family history of MTC or in patients with MEN 2 [see Warnings and Precautions ( 5.1 )] . • A prior serious hypersensitivity reaction to semaglutide or to any of the excipients in WEGOVY. Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with WEGOVY [see Warnings and Precautions ( 5.6 )]. • Personal or family history of MTC or in patients with MEN 2 ( 4 ). • Known hypersensitivity to semaglutide or any of the excipients in WEGOVY ( 4 ).

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 )] • Hypoglycemia [see Warnings and Precautions ( 5.4 )] • Acute Kidney Injury [see Warnings and Precautions ( 5.5 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.6 )] • Diabetic Retinopathy Complications in Patients with Type 2 Diabetes [see Warnings and Precautions ( 5.7 )] • Heart Rate Increase [see Warnings and Precautions ( 5.8 )] • Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.9 )] Most common adverse reactions (incidence ≥ 5%) in adults or pediatric patients aged 12 years and older are: nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, dyspepsia, dizziness, abdominal distension, eructation, hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis, gastroesophageal reflux disease, and nasopharyngitis ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc., at 1-833-934-6891 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. Adverse Reactions in Clinical Trials in Adults with Obesity or Overweight WEGOVY 2.4 mg Subcutaneous Weekly Dosage WEGOVY was evaluated for safety in 3 randomized, double-blind, placebo-controlled trials that included 2,116 adult patients with obesity or overweight treated with 2.4 mg WEGOVY for up to 68 weeks and a 7 week off-drug follow-up period [see Clinical Studies (14.2) ] . Baseline characteristics included a mean age of 48 years, 71% female, 72% White, 14% Asian, 9% Black or African American, and 5% reported as other or unknown; and 85% were not Hispanic or Latino ethnicity, 13% were Hispanic or Latino ethnicity, and 2% reported as unknown. The baseline characteristics were 42% with hypertension, 19% with type 2 diabetes, 43% with dyslipidemia, 28% with a BMI greater than 40 kg/m 2 , and 4% with cardiovascular disease. In these clinical trials, 6.8% of patients treated with 2.4 mg WEGOVY and 3.2% of patients treated with placebo permanently discontinued treatment as a result of adverse reactions. The most common adverse reactions leading to discontinuation were nausea (1.8% versus 0.2%), vomiting (1.2% versus 0%), and diarrhea (0.7% versus 0.1%) for WEGOVY and placebo, respectively. Adverse reactions reported in clinical trials in adults and greater than or equal to 2% of WEGOVY-treated patients and more frequently than in placebo-treated patients are shown in Table 3. Table 3. Adverse Reactions (≥2% and Greater Than Placebo) in WEGOVY-treated Adults with Obesity or Overweight Placebo N = 1,261 % WEGOVY 2.4 mg N = 2,116 % Nausea 16 44 Diarrhea 16 30 Vomiting 6 24 Constipation 11 24 Abdominal Pain a 10 20 Headache 10 14 Fatigue b 5 11 Dyspepsia 3 9 Dizziness 4 8 Abdominal Distension 5 7 Eructation <1 7 Hypoglycemia in T2DM c 2 6 Flatulence 4 6 Gastroenteritis 4 6 Gastroesophageal Reflux Disease 3 5 Gastritis d 1 4 Gastroenteritis Viral 3 4 Hair Loss 1 3 Dysesthesia e 1 2 a Includes abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain, abdominal tenderness, abdominal discomfort and epigastric discomfort b Includes fatigue and asthenia c Defined as blood glucose <54 mg/dL with or without symptoms of hypoglycemia or severe hypoglycemia (requiring the assistance of another person) in patients with type 2 diabetes not on concomitant insulin (Study 3, WEGOVY N=403, Placebo N=402). See text below for further information regarding hypoglycemia in patients with and without …

7 DRUG INTERACTIONS WEGOVY delays gastric emptying. May impact absorption of concomitantly administered oral medications. Use with caution ( 7.2 ). 7.1 Concomitant Use with Insulin or an Insulin Secretagogue (e.g., Sulfonylurea) WEGOVY lowers blood glucose and can cause hypoglycemia. The risk of hypoglycemia is increased when WEGOVY is used in combination with insulin or insulin secretagogues (e.g., sulfonylureas). The addition of WEGOVY in patients treated with insulin has not been evaluated. When initiating WEGOVY, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia [see Warnings and Precautions ( 5.4 ) and Adverse Reactions ( 6.1 )] . 7.2 Oral Medications WEGOVY causes a delay of gastric emptying and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials with semaglutide 1 mg, semaglutide did not affect the absorption of orally administered medications [see Clinical Pharmacology ( 12.3 )] . Nonetheless, monitor the effects of oral medications concomitantly administered with WEGOVY.

8 USE IN SPECIFIC POPULATIONS • Pregnancy: May cause fetal harm. When pregnancy is recognized, discontinue WEGOVY ( 8.1 ). • Females and Males of Reproductive Potential: Discontinue WEGOVY at least 2 months before a planned pregnancy because of the long half-life of semaglutide ( 8.3 ). 8.1 Pregnancy Pregnancy Exposure Registry There will be a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to semaglutide during pregnancy. Pregnant women exposed to WEGOVY and healthcare providers are encouraged to contact Novo Nordisk at 1-877-390-2760 or www.wegovypregnancyregistry.com. Risk Summary Based on animal reproduction studies, there may be potential risks to the fetus from exposure to semaglutide during pregnancy. 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 WEGOVY (see Clinical Considerations) . Available pharmacovigilance data and data from clinical trials with WEGOVY use in pregnant patients are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In pregnant rats administered semaglutide during organogenesis, embryofetal mortality, structural abnormalities and alterations to growth occurred at maternal exposures below the maximum recommended human dose (MRHD) based on AUC. In rabbits and cynomolgus monkeys administered semaglutide during organogenesis, early pregnancy losses and structural abnormalities were observed at below the MRHD (rabbit) and greater than or equal to 2-fold the MRHD (monkey). These findings coincided with a marked maternal body weight loss in both animal species (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. 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 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. Data Animal Data In a combined fertility and embryofetal development study in rats, subcutaneous doses of 0.01, 0.03 and 0.09 mg/kg/day (0.04-, 0.1-, and 0.4-fold the MRHD) were administered to males for 4 weeks prior to and throughout mating and to females for 2 weeks prior to mating, and throughout organogenesis to Gestation Day 17. In parental animals, pharmacologically mediated reductions in body weight gain and food consumption were observed at all dose levels. In the offspring, reduced growth and fetuses with visceral (heart blood vessels) and skeletal (cranial bones, vertebra, ribs) abnormalities were observed at the human exposure. In an embryofetal development study in pregnant rabbits, subcutaneous doses of 0.0010, 0.0025 or 0.0075 mg/kg/day (0.01-, 0.1-, and 0.9-fold the MRHD) were administered throughout organogenesis from Gestation Day 6 to 19. Pharmacologically mediated reductions in maternal body weight gain and food consumption were observed at all dose levels. Early pregnancy losses and increased incidences of minor visceral (kidney, liver) and skeletal (sternebra) fetal abnormalities were observed at greater than or equal to 0.0025 mg/kg/day, at clinically relevant exposures. In an embryofetal development study in pregnant cynomolgus monkeys, subcutaneous doses of 0.015, 0.075, and 0.15 mg/kg twice weekly (0.4-, 2-, and 6-fold the MRHD) were administered throughout organogenesis, from Gestation Day 16 to 50. Pharmacologically mediated, marked initial maternal body weight loss and reductions in body weight gain and food consumption coincided with the occurrence of sporadic abnorm …

12.1 Mechanism of Action Semaglutide is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1. GLP-1 is a physiological regulator of appetite and caloric intake, and the GLP-1 receptor is present in several areas of the brain involved in appetite regulation. Animal studies show that semaglutide distributed to and activated neurons in brain regions involved in regulation of food intake. The exact mechanism of cardiovascular risk reduction has not been established.

11 DESCRIPTION WEGOVY (semaglutide) injection, for subcutaneous use, contains semaglutide, a human GLP-1 receptor agonist (or GLP-1 analog). The peptide backbone is produced by yeast fermentation. The main protraction mechanism of semaglutide is albumin binding, facilitated by modification of position 26 lysine with a hydrophilic spacer and a C18 fatty di-acid. Furthermore, semaglutide is modified in position 8 to provide stabilization against degradation by the enzyme dipeptidyl-peptidase 4 (DPP-4). A minor modification was made in position 34 to ensure the attachment of only one fatty di-acid. The molecular formula is C 187 H 291 N 45 O 59 and the molecular weight is 4113.58 g/mol. Figure 1. Structural Formula of semaglutide WEGOVY is a sterile, aqueous, clear, colorless solution. Each 0.5 mL single-dose pen contains a solution of WEGOVY containing 0.25 mg, 0.5 mg or 1 mg of semaglutide; and each 0.75 mL single-dose pen contains a solution of WEGOVY containing 1.7 or 2.4 mg of semaglutide. Each 1 mL of WEGOVY contains the following inactive ingredients: disodium phosphate dihydrate, 1.42 mg; sodium chloride, 8.25 mg; and water for injection. WEGOVY has a pH of approximately 7.4. Hydrochloric acid or sodium hydroxide may be added to adjust pH. structural-formula

10 OVERDOSAGE Overdoses have been reported with other GLP-1 receptor agonists. Effects have included severe nausea, severe vomiting, and severe hypoglycemia. In the event of overdose, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms. In the event of an overdose of WEGOVY, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. A prolonged period of observation and treatment for these symptoms may be necessary, taking into account the long half-life of WEGOVY of approximately 1 week.

16 HOW SUPPLIED/STORAGE AND HANDLING Product: 50090-5824 NDC: 50090-5824-0 .5 mL in a SYRINGE, PLASTIC / 4 in a CARTON