Semaglutide

WEGOVY 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 injection 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, 2.4 mg or 7.2 mg of semaglutide. Each 0.5 mL single-dose prefilled syringe contains a solution of WEGOVY containing 0.25 mg, 0.5 mg or 1 mg of semaglutide; and each 0.75 mL single-dose prefilled syringe contains a solution of WEGOVY containing 1.7, 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. Each 3 mL prefilled single-patient-use pen contains semaglutide 9.6 mg (3.2 mg/mL), which provides 4 doses of 2.4 mg semaglutide per 0.75 mL. Each 1 mL of WEGOVY FlexTouch solution also contains the following inactive ingredients: disodium phosphate dihydrate, 1.42 mg; phenol, 5.5 mg; propylene glycol, 14 mg; and water for injections. WEGOVY has a pH of approximately 7.4. Hydrochloric acid or sodium hydroxide may be added to adjust pH. Each single-patient-use WEGOVY FlexTouch Pen contains additional volume to allow for device priming. WEGOVY tablets include semaglutide as a white to almost white hygroscopic powder. Each tablet of WEGOVY contains 1.5 mg, 4 mg, 9 mg or 25 mg of semaglutide and the following inactive ingredients: magnesium stearate and salcaprozate sodium (SNAC). structural-formula

WEGOVY injection is indicated in combination with a reduced calorie diet and increased physical activity: • to reduce the risk of major adverse cardiovascular (CV) events (CV death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established CV 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. • for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis) in adults. This indication is approved under accelerated approval based on improvement of MASH and fibrosis [see Clinical Studies ( 14.4 )] . Continued approval for this indication may be contingent upon the verification and description of clinical benefit in a confirmatory trial. WEGOVY tablets are indicated in combination with a reduced calorie diet and increased physical activity: • to reduce the risk of major adverse CV events (CV death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established CV disease and either obesity or overweight. • to reduce excess body weight and maintain weight reduction long term in adults with obesity, or in adults with overweight in the presence of at least one weight-related comorbid condition. Limitations of Use Concomitant use of WEGOVY (semaglutide) tablets or WEGOVY (semaglutide) injection 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. WEGOVY injection is indicated in combination with a reduced calorie diet and increased physical activity: • to reduce the risk of major adverse cardiovascular (CV) events (CV death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established CV 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. ( 1 ) o adults with overweight in the presence of at least one weight-related comorbid condition. ( 1 ) • for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis) in adults. This indication is approved under accelerated approval based on improvement of MASH and fibrosis. Continued approval for this indication may be contingent upon the verification and description of clinical benefit in a confirmatory trial. ( 1 ) WEGOVY tablets are indicated in combination with a reduced calorie diet and increased physical activity: • to reduce the risk of major adverse CV events (CV death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established CV disease and either obesity or overweight. ( 1 ) • to reduce excess body weight and maintain weight reduction long term in adults with obesity, or in adults with overweight in the presence of at least one weight-related comorbid condition. ( 1 ) Limitations of Use: • Concomitant use of WEGOVY (semaglutide) tablets or WEGOVY (semaglutide) injection with other semaglutide-containing products or with any other GLP-1 receptor agonist is not recommended. ( 1 )

WEGOVY Injection How Supplied WEGOVY injection is a clear, colorless solution available in cartons containing 4 single-dose pens, 4 single-dose syringes with integrated needles, or 1 single-patient-use pen (WEGOVY FlexTouch) as follows: Device Type Name Total Strength per Total Volume NDC Single-dose Pen WEGOVY 0.25 mg/0.5 mL 0169-4525-14 Single-dose Pen 0.5 mg/0.5 mL 0169-4505-14 Single-dose Pen 1 mg/0.5 mL 0169-4501-14 Single-dose Pen 1.7 mg/0.75 mL 0169-4517-14 Single-dose Pen 2.4 mg/0.75 mL 0169-4524-14 Single-dose Pen WEGOVY HD 7.2 mg/0.75 mL 0169-4572-14 Single-patient-use Pen (with 4 weekly doses of 2.4 mg) WEGOVY FlexTouch 9.6 mg/3 mL (3.2 mg/mL) 0169-4915-32 Single-dose Syringe WEGOVY 0.25 mg/0.5 mL 0169-1602-14 Single-dose Syringe 0.5 mg/0.5 mL 0169-1605-14 Single-dose Syringe 1 mg/0.5 mL 0169-1610-14 Single-dose Syringe 1.7 mg/0.75 mL 0169-1617-14 Single-dose Syringe 2.4 mg/0.75 mL 0169-1624-14 Recommended Storage • Do not store WEGOVY in the freezer or directly adjacent to the refrigerator cooling element. • Do not freeze WEGOVY and do not use if it has been frozen. Single-dose Pen or Single-dose Syringe Storage Store the WEGOVY prefilled single-dose pen or single-dose syringe in the refrigerator from 2°C to 8°C (36°F to 46°F). If needed, prior to the pen or syringe cap removal, the pen can be kept from 8°C to 30°C (46°F to 86°F) up to 28 days. Protect WEGOVY injection from light. WEGOVY injection must be kept in the original carton until time of administration. Discard the WEGOVY pen or syringe after use. Single-patient-use Pen (WEGOVY FlexTouch) Storage Prior to first use, store WEGOVY FlexTouch single-patient-use pen in a refrigerator between 2°C to 8°C (36°F to 46°F). After first use, WEGOVY FlexTouch single-patient-use pen can be stored for 56 days between 15°C to 30°C (59°F to 86°F) or in a refrigerator 2°C to 8°C (36°F to 46°F). WEGOVY FlexTouch single-patient-use pen should be protected from excessive heat and light. Keep the pen cap on when not in use. Always remove and safely discard the needle after each injection. Store the WEGOVY FlexTouch single-patient-use pen without an injection needle attached. Always use a new needle for each injection. WEGOVY Tablets How Supplied WEGOVY tablets are available as: Tablet strength Description Package Configuration NDC Number 1.5 mg White to light yellow, round shaped debossed with “1.5” on one side and “novo” on the other side Bottle of 30 tablets 0169-4415-31 4 mg White to light yellow, round shaped debossed with “4” on one side and “novo” on the other side Bottle of 30 tablets 0169-4404-31 9 mg White to light yellow, round shaped debossed with “9” on one side and “novo” on the other side Bottle of 30 tablets 0169-4409-31 25 mg White to light yellow, oval shaped debossed with “25” on one side and “novo” on the other side Bottle of 30 tablets 0169-4425-31 Recommended Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Store and dispense WEGOVY tablets in the original bottle. Store WEGOVY tablet in the original bottle until use to protect tablets from moisture. Store WEGOVY tablets in a dry place away from moisture.

In patients with diabetes, monitor blood glucose prior to starting and during WEGOVY treatment. ( 2.1 ) WEGOVY Injection • Administer WEGOVY injection 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 ) • Initiate at 0.25 mg once weekly for 4 weeks. Then follow the dosage escalation schedule in Table 1, titrating every 4 weeks to achieve the maintenance dosage. ( 2.2 ) • The usual recommended maintenance dosage of WEGOVY injection is 2.4 mg once weekly. Refer to the full PI for maintenance dosages based on the indication. ( 2.2 ) WEGOVY Tablets • Take WEGOVY tablets orally once-daily on an empty stomach in the morning with water (up to 4 ounces). Do not take with other liquids besides water. ( 2.1 ) • Swallow tablets whole. Do not split, crush, chew or dissolve. ( 2.1 ) • After taking WEGOVY tablet wait at least 30 minutes before eating food, drinking beverages or taking other oral medications. ( 2.1 ) • Initiate WEGOVY tablet with a dosage of 1.5 mg once daily for 30 days. Then follow the dosage escalation schedule, titrating every 30 days to achieve the maintenance dosage. ( 2.2 ) • The recommended maintenance dosage of WEGOVY tablets is 25 mg orally once daily for cardiovascular risk reduction and weight reduction in adults. ( 2.3 ) 2.1 Important Monitoring and Administration Instructions In patients with diabetes mellitus, monitor blood glucose prior to starting WEGOVY and during WEGOVY treatment [see Warnings and Precautions (5.4 )] . Administer WEGOVY in combination with a reduced-calorie diet and increased physical activity. WEGOVY Injection • Inform patients and their caregiver(s) which WEGOVY presentation (e.g., single-dose pen or syringe, or WEGOVY FlexTouch single-patient-use pen) they will receive and ensure they receive training appropriate for that specific presentation. If the prescribed WEGOVY presentation changes, ensure patients and caregivers receive appropriate training and instruct them to consult the Instructions for Use for the newly prescribed presentation. • Prior to initiation, train patients and their caregiver(s) on proper injection technique for the prescribed WEGOVY presentation [see Instructions for Use ] . After training, a patient may self-inject WEGOVY if the healthcare provider determines that it can be properly administered, except for the following: o WEGOVY FlexTouch is not recommended for self-administration by those who are visually impaired. • Visually inspect the WEGOVY injection prior to each administration. Only use if the solution is clear, colorless, and contains no particles. • Administer WEGOVY injection 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 the need for a dosage modification. • Rotate injection sites with each dose. WEGOVY Tablets • Take one WEGOVY tablet orally once daily on an empty stomach in the morning with water (up to 4 ounces). Do not take WEGOVY tablets with other liquids besides water [see Clinical Pharmacology ( 12.3 )] . • Swallow tablets whole. Do not split, crush, chew or dissolve in any solution. • Do not take more than one tablet per day. • After taking a WEGOVY tablet, wait at least 30 minutes before eating food, drinking beverages or taking other oral medications [see Clinical Pharmacology ( 12.3 )] . 2.2 Recommended Dosage for WEGOVY Injection Recommended Starting Dosage and Dosage Escalation of WEGOVY Injection for All Approved Indications • The recommended starting dosage of WEGOVY injection is 0.25 mg administered subcutaneously once weekly. • Follow the dosage escalation in Table 1 to reduce the risk of gastrointestinal adverse reactions [see Warnings and Precautions ( 5.6 ), Adverse Reactions ( 6.1 )] . • If patients do not tolerate a dose during dosage escalation, consider delaying dosage escalation for 4 weeks. Table 1. Recommended Starting Dosage and Dosage Escalation of WEGOVY Injection for All Approved Indications in Adults and Pediatric Patients Aged 12 Years and Older Weeks Once-weekly Subcutaneous Injection Dosage Starting Dosage 1 through 4 0.25 mg Dosage Escalation 5 through 8 0.5 mg 9 through 12 1 mg 13 through 16 1.7 mg Maintenance Dosage 17 and onward See the indication below for the recommended maintenance dosage(s) Recommended Maintenance Dosage of WEGOVY Injection for All Approved Indications Cardiovascular Risk Reduction in Adults • The maintenance dosage of WEGOVY injection for cardiovascular risk reduction 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 Adverse Reactions ( 6.1 ), Clinical Studies ( 14.1 )] . Weight Reduction in Adults • The maintenance dosage of WEGOVY for weight reduction in adults is either 1.7 mg or 2.4 mg (recommended) injected subcutaneously once weekly. • For patients who tolerate the 2.4 mg dosage for at least 4 weeks and additional weight reduction is clinically indicated, the dosage may be increased to a maximum dosage of 7.2 mg subcutaneously once weekly. • Consider treatment response and tolerability when selecting the maintenance dosage [see Adverse Reactions ( 6.1 ), Clinical Studies ( 14.2 )]. Weight Reduction in Pediatric Patients Aged 12 Years and Older • The maintenance dosage of WEGOVY injection for weight reduction in pediatric patients aged 12 years and older is either 2.4 mg (recommended), or 1.7 mg once weekly. • Consider treatment response and tolerability when selecting the maintenance dosage [see Adverse Reactions ( 6.1 ), Clinical Studies ( 14.3 )] . Noncirrhotic MASH with Moderate to Advanced Liver Fibrosis in Adults • The recommended maintenance dosage of WEGOVY injection for the treatment of noncirrhotic MASH with moderate to advanced liver fibrosis in adults is 2.4 mg injected subcutaneously once weekly. If patients do not tolerate the maintenance dosage of 2.4 mg once weekly, the dosage can be decreased to 1.7 mg once weekly. Consider reescalation to 2.4 mg once weekly [see Adverse Reactions ( 6.1 ), Clinical Studies ( 14.4 )] . 2.3 Recommended Dosage of WEGOVY Tablets Recommended Dosage of WEGOVY Tablets for Cardiovascular Risk Reduction or Weight Reduction in Adults • The recommended starting dosage of WEGOVY tablets is 1.5 mg taken orally once daily. Follow the dosage escalation in Table 2 to reduce the risk of gastrointestinal adverse reactions [see Warnings and Precautions ( 5.6 ), Adverse Reactions ( 6.1 )] . • If patients do not tolerate a dose during dosage escalation, consider delaying dosage escalation. • The recommended maintenance dosage of WEGOVY tablets is 25 mg orally once daily. • If patients do not tolerate the 25 mg once daily maintenance dosage, consider switching to WEGOVY injection 1.7 mg once weekly [see Dosage and Administration ( 2.5 )] . Table 2. Recommended Dosage of WEGOVY Tablets for Cardiovascular Risk Reduction or Weight Reduction in Adults Days Once Daily Tablet Dosage Starting Dosage 1 through 30 1.5 mg Dosage Escalation 31 through 60 4 mg 61 through 90 9 mg Maintenance Dosage 91 and onward 25 mg 2.4 Recommendations Regarding Missed Dose(s) WEGOVY Injection • If one dose of WEGOVY injection is missed and the next scheduled dose is: o more than 2 days away, administer WEGOVY injection as soon as possible. o less than 2 days away, do not administer the WEGOVY injection dose. Resume dosing on the regularly scheduled day of the week. • If 2 or more consecutive doses of WEGOVY injection are missed, reinitiate dosage escalation at a lower dosage to reduce the risk of gastrointestinal adverse reactions [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.6 ), Adverse Reactions (6.1)]. WEGOVY Tablets If a dose of WEGOVY tablets is missed, skip the missed dose and take the next dose the following day. 2.5 Switching Between WEGOVY Injection and WEGOVY Tablets Switching from WEGOVY Injection to WEGOVY Tablets • Patients taking WEGOVY 2.4 mg injection for cardiovascular risk reduction or weight reduction in adults may switch to WEGOVY 25 mg tablets. • One week after discontinuing WEGOVY 2.4 mg injection, initiate 25 mg of WEGOVY tablets orally once daily. Switching from WEGOVY Tablets to WEGOVY Injection • Patients may switch from WEGOVY 25 mg tablets to WEGOVY injection. • The day after discontinuing WEGOVY tablets 25 mg once daily, initiate WEGOVY 2.4 mg subcutaneous injection once weekly. For patients who do not tolerate WEGOVY 25 mg tablets, consider switching to WEGOVY 1.7 mg injection. • If additional weight reduction is needed in patients with type 2 diabetes mellitus treated with WEGOVY 25 mg tablets, consider switching to WEGOVY 1.7 mg injection and follow the recommended dosage escalation for WEGOVY injection [see Dosage and Administration ( 2.2 ), Use in Specific Populations ( 8.6 ), Clinical Pharmacology ( 12.3 )].

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 injection or WEGOVY tablet. Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with WEGOVY [see Warnings and Precautions ( 5.7 )] . • Personal or family history of MTC or in patients with MEN 2. ( 4 ) • Known hypersensitivity to semaglutide or any of the excipients in WEGOVY tablets or WEGOVY injection. ( 4 )

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Risk of Thyroid C-cell Tumors Inform patients that semaglutide causes thyroid C-cell tumors in rodents 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 physician [see Boxed Warning, Warnings and Precautions ( 5.1 )] . Acute Pancreatitis Inform patients of the potential risk for acute pancreatitis and its symptoms: severe abdominal pain that sometimes radiates to the back, and which may or may not be accompanied by nausea or vomiting. Instruct patients to discontinue WEGOVY promptly and contact their physician if pancreatitis is suspected [see Warnings and Precautions ( 5.2 )] . Acute Gallbladder Disease 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 Inform patients of the risk of hypoglycemia and educate patients on the signs and symptoms of hypoglycemia. Advise patients with diabetes mellitus on glycemic lowering therapy that they may have an increased risk of hypoglycemia when using WEGOVY and to report signs and/or symptoms of hypoglycemia to their healthcare provider [see Warnings and Precautions ( 5.4 )] . Acute Kidney Injury due to Volume Depletion 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 persistent (or extended) nausea, vomiting, and diarrhea to their healthcare provider [see Warnings and Precautions ( 5.5 )] . Severe Gastrointestinal Adverse Reactions 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 ( 5.6 )]. Hypersensitivity Reactions Inform patients that serious hypersensitivity reactions have been reported during postmarketing use of semaglutide, the active ingredient in WEGOVY. Advise patients on the symptoms of hypersensitivity reactions and instruct them to stop taking WEGOVY and seek medical advice promptly if such symptoms occur [see Warnings and Precautions ( 5.7 )] . Diabetic Retinopathy Complications in Patients with Type 2 Diabetes Inform patients with type 2 diabetes to contact their physician if changes in vision are experienced during treatment with WEGOVY [see Warnings and Precautions ( 5.8 )] . Heart Rate Increase Instruct patients to inform their healthcare providers of palpitations or feelings of a racing heartbeat while at rest during WEGOVY treatment [see Warnings and Precautions ( 5.9 )] . Pulmonary Aspiration During General Anesthesia or Deep Sedation Inform patients that WEGOVY 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 WEGOVY [see Warnings and Precautions ( 5.10 )]. Never Share a WEGOVY FlexTouch Pen Between Patients Advise patients that they must never share a WEGOVY FlexTouch 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 ( 5.11 )] . Pregnancy WEGOVY may cause fetal harm. Advise patients to inform their healthcare provider of a known or suspected pregnancy. Advise patients who are exposed to WEGOVY during pregnancy to contact Novo Nordisk at 1-877-390-2760 or www.wegovypregnancyregistry.com [see Use in Specific Populations ( 8.1 )] . Administration Instruct patients how to prepare and administer the correct dose of WEGOVY and assess their ability to inject subcutaneously to ensure the proper administration of WEGOVY. Inform patients and their caregiver(s) which WEGOVY presentation (e.g., single-dose pen or syringe, WEGOVY FlexTouch single-patient-use pen) they will receive and ensure they receive training appropriate for that specific presentation. If the prescribed WEGOVY presentation changes, ensure patients and caregivers receive appropriate training and instruct them to consult the Instructions for Use for the newly prescribed presentation. Advise caregivers that WEGOVY FlexTouch is not recommended for self-administration by those with visual impairment unless their healthcare provider determines the patient can properly administer [see Dosage and Administration ( 2.1 )]. Missed Doses Inform patients if a dose of WEGOVY injection is missed and the next scheduled dose is more than 2 days away (48 hours), administer WEGOVY injection 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 the dose. Inform patients to resume their regular once-weekly dosing schedule [see Dosage and Administration ( 2.4 )]. Inform patients if a dose of WEGOVY tablets is missed, skip the missed dose and take the next dose the following day [see Dosage and Administration ( 2.4 )] . Lactation Advise females not to breastfeed during treatment with WEGOVY tablets [see Use in Specific Populations ( 8.2 )] . Marketed by: Novo Nordisk Inc., Plainsboro, NJ 08536 For additional information about WEGOVY contact: Novo Nordisk Inc. 800 Scudders Mill Road Plainsboro, NJ 08536 1-833-934-6891 WEGOVY ® and FlexTouch ® are registered trademarks of Novo Nordisk A/S. Patent Information: http://www.novonordisk-us.com/products/product-patents.html © 2026 Novo Nordisk

WEGOVY delays gastric emptying. May impact absorption of concomitantly administered oral medications. Consider increased clinical or laboratory monitoring when used concomitantly with other oral medications that have a narrow therapeutic index or that require clinical monitoring. ( 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 concomitantly 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 or insulin to reduce the risk of hypoglycemia [see Warnings and Precautions ( 5.4 ), 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 once weekly injection, semaglutide did not affect the absorption of orally administered medications [see Clinical Pharmacology ( 12.3 )] . In a drug interaction study with the semaglutide tablet, levothyroxine exposure was increased 33% (90% CI: 1.25-1.42). Monitor the effects of oral medications concomitantly administered with WEGOVY. Consider increased clinical or laboratory monitoring for medications that have a narrow therapeutic index or that require clinical monitoring.

In a 2-year carcinogenicity study in CD-1 mice, subcutaneous semaglutide doses of 0.3, 1 and 3 mg/kg/day (up to 7-fold the MRHD of WEGOVY subcutaneous injection 7.2 mg/week, based on AUC) were administered to the males, and 0.1, 0.3 and 1 mg/kg/day (up to 2-fold MRHD) were administered to the females. A statistically significant increase in thyroid C-cell adenomas and a numerical increase in C-cell carcinomas were observed in males and females at all dose levels, at clinically relevant exposures. In a 2-year carcinogenicity study in Sprague Dawley rats, subcutaneous semaglutide doses of 0.0025, 0.01, 0.025 and 0.1 mg/kg/day were administered (up to 0.7-fold the exposure at the MRHD). A statistically significant increase in thyroid C-cell adenomas was observed in males and females at all dose levels, and a statistically significant increase in thyroid C-cell carcinomas was observed in males at greater than or equal to 0.01 mg/kg/day, at clinically relevant exposures. Human relevance of thyroid C-cell tumors in rats is unknown and could not be determined by clinical studies or nonclinical studies [see Warnings and Precautions ( 5.1 )] . Semaglutide was not mutagenic or clastogenic in a standard battery of genotoxicity tests (i.e., bacterial mutagenicity [Ames], human lymphocyte chromosome aberration, rat bone marrow micronucleus). In a combined fertility and embryo-fetal development study in rats, subcutaneous semaglutide doses of 0.01, 0.03 and 0.09 mg/kg/day (up to 0.1-fold the MRHD) were administered to male and female rats. Males were dosed for 4 weeks prior to mating, and females were dosed for 2 weeks prior to mating and throughout organogenesis until Gestation Day 17. No effects were observed on male fertility. In females, an increase in estrus-cycle length was observed at all dose levels, together with a small reduction in numbers of corpora lutea at greater than or equal to 0.03 mg/kg/day, at clinically relevant exposures. These effects were likely an adaptive response secondary to the pharmacological effect of semaglutide on food consumption and body weight.

Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to WEGOVY 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. 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. 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. Discontinue WEGOVY in pregnant patients who are using it for weight reduction (see Clinical Considerations ). There may be risks to the mother and fetus related to underlying MASH with advanced liver fibrosis (see Clinical Considerations ). Whether WEGOVY treatment during pregnancy reduces these risks is unknown. WEGOVY for the treatment of MASH with advanced liver fibrosis should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In pregnant rats administered semaglutide during organogenesis, embryofetal mortality, structural abnormalities and alterations to growth occurred at clinically relevant maternal exposures at the maximum recommended human dose (MRHD) of WEGOVY subcutaneous injection 7.2 mg/week, based on AUC. In pregnant rabbits and cynomolgus monkeys administered semaglutide during organogenesis, early pregnancy losses and structural abnormalities were observed in rabbits and monkeys at clinically relevant exposures. These findings coincided with a marked maternal body weight loss in both animal species (see Data ). The background risk of major birth defects and miscarriage for the indicated populations are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 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. There may be risks to the mother and fetus related to MASH with advanced liver fibrosis, such as increased risks of gestational diabetes, hypertensive complications, preterm birth, and postpartum hemorrhage. The effect of WEGOVY on these risks is unknown. Data Animal Data: In a combined fertility and embryofetal development study in male and female rats, subcutaneous semaglutide doses of 0.01, 0.03, and 0.09 mg/kg/day (up to 0.1-fold the MRHD, based on AUC) were administered to male rats for 4 weeks prior to and throughout mating and to female rats for 2 weeks prior to mating, and throughout organogenesis to Gestation Day 17. In parental rats, 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 clinically relevant exposures at the MRHD. In an embryofetal development study in pregnant rabbits, subcutaneous semaglutide doses of 0.001, 0.0025, or 0.0075 mg/kg/day (up to 0.3-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 at the MRHD. In an embryofetal development study in pregnant cynomolgus monkeys, subcutaneous semaglutide doses of 0.015, 0.075, and 0.15 mg/kg twice weekly (up to 2-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 abnormalities (vertebra, sternebra, ribs) at greater than or equal to 0.075 mg/kg twice weekly, at clinically relevant exposures at the MRHD. In a pre- and postnatal development study in pregnant cynomolgus monkeys, subcutaneous semaglutide doses of 0.015, 0.075, and 0.15 mg/kg twice weekly (up to 0.8-fold the MRHD) were administered from Gestation Day 16 to 140. Pharmacologically mediated marked initial maternal body weight loss and reductions in body weight gain and food consumption coincided with an increase in early pregnancy losses and led to delivery of slightly smaller offspring at greater than or equal to 0.075 mg/kg twice weekly, at clinically relevant exposures at the MRHD. Salcaprozate sodium (SNAC), an absorption enhancer in WEGOVY tablets, crosses the placenta and reaches fetal tissues in rats. In a pre- and postnatal development study in pregnant Sprague Dawley rats, SNAC was administered orally at 1,000 mg/kg/day (exposure levels were not measured) on Gestation Day 7 through lactation Day 20. An increase in gestation length, an increase in the number of stillbirths and a decrease in pup viability were observed.

The safety and effectiveness of WEGOVY injection in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in pediatric patients aged 12 years and older with obesity have been established. Use of WEGOVY injection for this indication is supported by a 68-week, double-blind, placebo-controlled clinical trial in 201 pediatric patients aged 12 years and older with a BMI corresponding to ≥95th percentile for age and sex [see Clinical Studies ( 14.3 )] and from trials in adult patients with obesity [see Clinical Studies ( 14.2 )] . Use of the 1.7 mg once weekly maintenance dosage of WEGOVY injection in pediatric patients is also supported by additional exposure-efficacy and safety analyses in pooled adult and pediatric patients. Adverse reactions with WEGOVY injection treatment in pediatric patients aged 12 years and older were generally similar to those reported in adults. Pediatric patients aged 12 years and older treated with WEGOVY injection had greater incidences of cholelithiasis, cholecystitis, hypotension, rash, and urticaria compared to adults treated with WEGOVY [see Adverse Reactions ( 6.1 )] . Although there was an increased frequency of hypoglycemia in adults with type 2 diabetes with obesity or overweight treated with WEGOVY injection, there are insufficient data to determine if the risk of hypoglycemia is higher in WEGOVY-treated pediatric patients with type 2 diabetes with obesity. Inform pediatric patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia. In pediatric patients aged 12 years and older with type 2 diabetes, monitor blood glucose prior to starting WEGOVY injection and during treatment. When initiating WEGOVY injection in pediatric patients aged 12 years and older with type 2 diabetes, consider reducing the dosage of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia [see Warnings and Precautions ( 5.4 )] . The safety and effectiveness of WEGOVY injection have not been established in pediatric patients: • to reduce the risk of major adverse CV events. Clinical trials for this indication are highly impracticable because of the low prevalence of the condition in pediatric patients. • to reduce excess body weight and maintain weight reduction long term with the 7.2 mg once weekly dosage. • to reduce excess body weight and maintain weight reduction long term in those less than 12 years of age. • for the treatment of noncirrhotic MASH. The safety and effectiveness of WEGOVY tablets have not been established in pediatric patients.

In the WEGOVY injection clinical trials for weight reduction and long-term maintenance, 233 (9%) WEGOVY injection-treated patients were aged 65 to less than 75 years and 23 (1%) WEGOVY injection-treated patients were aged 75 years and older [see Clinical Studies ( 14.2 )] . In a WEGOVY 25 mg tablets clinical trial for weight reduction and long-term maintenance, 16 (8%) WEGOVY tablets-treated patients were aged 65 to less than 75 years and 5 (2%) WEGOVY tablet-treated patients were aged 75 years and older [see Clinical Studies ( 14.2 )] . In a CV outcomes trial, 2,656 (30%) WEGOVY injection-treated patients were aged 65 to 75 years and 703 (8%) WEGOVY injection-treated patients were aged 75 years and older [see Clinical Studies ( 14.1 )] . No overall difference in the effectiveness was observed between patients aged 65 years and older and younger adult patients. In the CV outcomes trial, patients aged 75 years and older reported more hip and pelvis fractures in the WEGOVY injection-treated patients than placebo-treated patients. Patients aged 75 years and older (WEGOVY injection-treated and placebo-treated) reported more serious adverse reactions overall compared to younger adult patients [see Adverse Reactions ( 6.1 )] . In the clinical trial in patients with MASH, of the 534 patients randomized to WEGOVY injection, 138 (26%) were aged 65 years and older and 13 (2%) were aged 75 years and older [see Clinical Studies ( 14.4 )] . No overall differences in safety or effectiveness of WEGOVY injection have been observed between patients 65 years of age and older and younger adult patients with MASH.

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 Due to Volume Depletion [see Warnings and Precautions ( 5.5 )] • Severe Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.6 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.7 )] • Diabetic Retinopathy Complications in Patients with Type 2 Diabetes [see Warnings and Precautions ( 5.8 )] • Heart Rate Increase [see Warnings and Precautions ( 5.9 )] • Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions ( 5.10 )] Most common adverse reactions (incidence ≥5%) in adults or pediatric patients aged 12 years and older are: nausea, diarrhea, vomiting, constipation, abdominal pain, dysesthesia, headache, fatigue, dyspepsia, dizziness, abdominal distension, eructation, hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis, gastroesophageal reflux disease, and hair loss. ( 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 for Weight Reduction WEGOVY 2.4 mg Subcutaneous Injection 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 injection 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 CV disease. In these clinical trials, 6.8% of patients treated with 2.4 mg WEGOVY injection 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. Table 3 shows adverse reactions reported in greater than or equal to 2% of WEGOVY 2.4 mg injection-treated adult patients and more frequently than in the placebo group from these trials. Table 3. Adverse Reactions (≥2% and Greater Than Placebo) in WEGOVY 2.4 mg Injection-treated Adults with Obesity or Overweight for Weight Reduction Placebo N=1,261 % WEGOVY Injection (2.4 mg Once Weekly) 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 type 2 diabetes. T2DM = type 2 diabetes mellitus. d Includes chronic gastritis, gastritis, gastritis erosive, and reflux gastritis. e Includes paresthesia, hyperesthesia, burning sensation, allodynia, dysesthesia, skin burning sensation, pain of skin, and sensitive skin. CV Outcomes Trial In a CV outcomes trial, 8,803 patients were exposed to WEGOVY injection for a median of 37.3 months and 8,801 patients were exposed to placebo for a median of 38.6 months [see Clinical Studies ( 14.1 )] . Safety data collection was limited to serious adverse events (including death), adverse events leading to discontinuation, and adverse events of special interest. Sixteen percent (16%) of WEGOVY injection-treated patients and 8% of placebo-treated patients, respectively, discontinued study drug due to an adverse event. Additional information from this trial is included in subsequent sections below when relevant. WEGOVY 7.2 mg Subcutaneous Injection Weekly Dosage The safety of WEGOVY 7.2 mg injection was evaluated in two 72-week double-blinded randomized placebo-controlled 3-armed trials (Study 8 and Study 9), including 1,311 patients with obesity (BMI ≥30 kg/m 2 ) exposed in the treatment arm with WEGOVY 7.2 mg injection, 304 patients exposed in the treatment arm with WEGOVY 2.4 mg injection, and 303 patients exposed to placebo [see Clinical Studies ( 14.2 )] . After dosage escalation, 1,149 patients received at least one dose of WEGOVY 7.2 mg injection, and 578 patients received 7.2 mg for at least 1 year. Baseline characteristics in the WEGOVY 7.2 mg injection arm included a mean age of 49 years, 70% female, 85% White, 5% Asian, 8% Black or African American, and 2% reported as other or unknown; and 5% were Hispanic or Latino ethnicity. At baseline, mean BMI was 39.5 kg/m 2 , 52% with hypertension, 38% with dyslipidemia, 40% with a BMI greater than 40 kg/m 2 , and 14% with CV disease. In these clinical trials, 5% of patients treated with 7.2 mg WEGOVY injection, 5% of patients treated with 2.4 mg of WEGOVY injection and 2% of patients treated with placebo permanently discontinued treatment as a result of adverse reactions. The most common adverse reactions leading to discontinuation were gastrointestinal disorders: 3%, 3%, and 0.3%, for WEGOVY 7.2 mg injection, WEGOVY 2.4 mg injection, and placebo, respectively. Table 4 shows adverse reactions reported in greater than or equal to 2% of WEGOVY 7.2 mg injection and more frequently than 2.4 mg injection-treated and placebo-treated patients from these studies. Table 4. Adverse Reactions (2% and Greater Than WEGOVY 2.4 mg and Placebo) in WEGOVY 7.2 mg Injection-treated Adults with Obesity for Weight Reduction Placebo N=303 % WEGOVY Injection (2.4 mg Once Weekly) N=304 % WEGOVY Injection (7.2 mg Once Weekly) N=1,311 % Nausea 13 35 39 Vomiting 6 16 22 Dysesthesia a 0 6 22 Constipation 8 19 20 Abdominal pain b 7 9 12 Fatigue c 5 9 11 Headache 7 8 9 Dizziness d 1 5 6 Hair loss 1 3 6 Flatulence 2 2 4 a Includes allodynia, burning sensation, dysesthesia, hyperesthesia, hyperpathia, pain of skin, paresthesia, sensitive skin, skin burning sensation, skin discomfort, and skin sensitization. b Includes abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain, abdominal tenderness, abdominal discomfort and epigastric discomfort. c Includes fatigue and asthenia. d Includes dizziness and dizziness postural. WEGOVY Tablet 25 mg Oral Daily Dosage WEGOVY tablet was evaluated for safety in a randomized, double-blind, placebo-controlled trial that included 204 adult patients with obesity or overweight and at least one weight-related comorbidity, treated with WEGOVY 25 mg tablets for up to 64 weeks and a 7-week off drug follow-up period (Study 7) [see Clinical Studies ( 14.2 )] . Patients with type 2 diabetes mellitus were excluded. Baseline characteristics included a mean age of 48 years, 76% were female, 93% were White, 0.5% were Asian, 6% were Black or African American, and 8% were Hispanic or Latino ethnicity. Mean baseline body weight was 106.4 kg and mean BMI was 37.5 kg/m 2 . The baseline characteristics were 44% with hypertension, 31% with dyslipidemia, 27% with a BMI greater than 40 kg/m 2 and 1.5% with coronary artery disease. In the clinical trial, 6.9% of patients treated with WEGOVY 25 mg tablets and 5.9% patients treated with placebo permanently discontinued treatment as a result of adverse reactions. The most common event type leading to discontinuation was gastrointestinal adverse reactions reported in 3.4% with WEGOVY tablets and 2% with placebo. In the clinical trial with WEGOVY 25 mg tablets, the types and frequency of common adverse reactions were similar to those listed in Table 3 . Adverse Reactions in a Clinical Trial of Pediatric Patients Aged 12 Years and Older with Obesity Treated with WEGOVY 2.4 mg Injection for Weight Reduction WEGOVY injection was evaluated in a 68-week, double-blind, randomized, parallel group, placebo-controlled, multi-center trial in 201 pediatric patients aged 12 years and older with obesity [see Clinical Studies ( 14.3 )] . Baseline characteristics included a mean age of 15.4 years; 38% of patients were male; 79% were White, 8% were Black or African American, 2% were Asian, and 11% were of other or unknown race; and 11% were of Hispanic or Latino ethnicity. The mean baseline body weight was 107.5 kg, and mean BMI was 37 kg/m 2 . Table 5 shows adverse reactions reported in greater than or equal to 3% of WEGOVY injection-treated pediatric patients and more frequently than in the placebo group from a trial in pediatric patients aged 12 years and older. Table 5. Adverse Reactions (≥3% and Greater than Placebo) in WEGOVY 2.4 mg Injection-treated Pediatric Patients Aged 12 Years and Older with Obesity for Weight Reduction Placebo N=67 % WEGOVY Injection (2.4 mg Once Weekly) N=133 % Nausea 18 42 Vomiting 10 36 Diarrhea 19 22 Headache 16 17 Abdominal Pain 6 15 Nasopharyngitis 10 12 Dizziness 3 8 Gastroenteritis 3 7 Constipation 2 6 Gastroesophageal Reflux Disease 2 4 Sinusitis 2 4 Urinary tract infection 2 4 Ligament sprain 2 4 Anxiety 2 4 Hair Loss 0 4 Cholelithiasis 0 4 Eructation 0 4 Influenza 0 3 Rash 0 3 Urticaria 0 3 Adverse Reactions in Clinical Trials in Adults with MASH Treated with WEGOVY Injection The safety of WEGOVY injection was evaluated in a randomized, double-blind, placebo-controlled trial (Study 11) that included 1,195 adult patients with MASH, including 800 patients who were exposed to WEGOVY for a median of 95.3 weeks and 395 patients who were exposed to placebo for a median of 83.1 weeks [see Clinical Studies ( 14.4 )]. The most commonly reported adverse reactions were consistent with the other approved WEGOVY indications (see Table 3 ). There is limited information in patients with MASH and a BMI <25 kg/m 2 . Additional information from the MASH trial is included in subsequent sections when notable. Unless indicated, the incidence of the adverse reactions in MASH patients was similar to other approved indications. Other Adverse Reactions in Adults and/or Pediatric Patients Treated with WEGOVY Injection or WEGOVY Tablets The safety of WEGOVY tablets and WEGOVY 7.2 mg injection have not been established in pediatric patients or patients with MASH. Acute Gallbladder Disease In WEGOVY clinical trials in adults for weight reduction, cholelithiasis was reported by 1.6% of WEGOVY injection-treated patients and 0.7% of placebo-treated patients and by 2.5% of WEGOVY tablet-treated patients and 1% of placebo tablet-treated patients. Cholecystitis was reported by 0.6% of WEGOVY injection-treated adult patients and 0.2% of placebo-treated patients. In a clinical trial in pediatric patients aged 12 years and older for weight reduction [see Clinical Studies ( 14.3 )] , cholelithiasis was reported by 3.8% of WEGOVY injection-treated patients and 0% placebo-treated patients. Cholecystitis was reported by 0.8% of WEGOVY injection-treated pediatric patients and 0% placebo-treated patients. Hypoglycemia Patients with Type 2 Diabetes In a trial of adult patients with type 2 diabetes and BMI greater than or equal to 27 kg/m 2 for weight reduction, clinically significant hypoglycemia (defined as a plasma glucose less than 54 mg/dL) was reported in 6.2% of WEGOVY injection-treated patients versus 2.5% of placebo-treated patients. A higher rate of clinically significant hypoglycemic episodes was reported with WEGOVY injection (semaglutide 2.4 mg) versus semaglutide 1 mg injection (10.7 vs. 7.2 episodes per 100 patient years of exposure, respectively); the rate in the placebo-treated group was 3.2 episodes per 100 patient years of exposure. In addition, one episode of severe hypoglycemia requiring intravenous glucose was reported in a WEGOVY injection-treated patient versus none in placebo-treated patients. The risk of hypoglycemia was increased when WEGOVY was used with a sulfonylurea. In a glycemic control trial evaluating a dose comparable to the 9 mg and 25 mg semaglutide tablet dose in patients with type 2 diabetes not on insulin, clinically significant hypoglycemia was reported in similar proportions of subjects in both treatment groups. Patients without Type 2 Diabetes Episodes of hypoglycemia have been reported with GLP-1 receptor agonists in adult patients without type 2 diabetes mellitus. In WEGOVY clinical trials in adult patients without type 2 diabetes mellitus for weight reduction, there was no systematic capturing or reporting of hypoglycemia. In a CV outcomes trial in adult patients without type 2 diabetes, 3 episodes of serious hypoglycemia were reported in WEGOVY injection-treated patients versus 1 episode in placebo. Patients with a history of bariatric surgery (a risk factor for hypoglycemia) had more events of serious hypoglycemia while taking WEGOVY injection (2.3%, 2/87) than placebo (0%, 0/97). Retinal Disorders in Patients with Type 2 Diabetes In a trial of adult patients with type 2 diabetes and BMI greater than or equal to 27 kg/m 2 for weight reduction, retinal disorders were reported by 6.9% of patients treated with WEGOVY injection (semaglutide 2.4 mg), 6.2% of patients treated with semaglutide 1 mg, and 4.2% of patients treated with placebo. The majority of events were reported as diabetic retinopathy (4%, 2.7%, and 2.7%, respectively) and non-proliferative retinopathy (0.7%, 0%, and 0%, respectively). In a glycemic control trial evaluating the 9 mg and 25 mg semaglutide tablet doses in patients with type 2 diabetes, a similar proportion of patients in each dose group reported diabetic retinopathy related adverse reactions during the trial; 1.3% and 1.9% of patients in the 9 mg and 25 mg semaglutide group, respectively, reported moderate-severe non-proliferative diabetic retinopathy events, and 0% and 0.4% reported proliferative retinopathy events, respectively. In a 2-year trial with semaglutide 0.5 mg and 1 mg once-weekly injection in adult patients with type 2 diabetes and high cardiovascular risk, diabetic retinopathy complications (which was a 4-component adjudicated endpoint) occurred in patients treated with semaglutide injection (3%) compared to placebo (1.8%). The absolute risk increase for diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy at baseline (semaglutide injection 8.2%, placebo 5.2%) than among patients without a known history of diabetic retinopathy (semaglutide injection 0.7%, placebo 0.4%). Gastrointestinal Adverse Reactions In clinical trials in adults for weight reduction, 73% of WEGOVY injection-treated patients and 47% of patients receiving placebo reported gastrointestinal adverse reactions, including severe reactions that were reported more frequently among patients receiving WEGOVY injection (4.1%) than placebo (0.9%). The most frequently reported reactions were nausea (44% vs. 16%), vomiting (25% vs. 6%), and diarrhea (30% vs. 16%). Other reactions that occurred at a higher incidence among WEGOVY injection-treated adult patients included dyspepsia, abdominal pain, abdominal distension, eructation, flatulence, gastroesophageal reflux disease, gastritis, hemorrhoids, and hiccups. These reactions were most frequently reported during dosage escalation. Severe gastrointestinal adverse reactions were reported in 2% of WEGOVY tablet-treated and 0% of placebo-treated patients, respectively. In the pediatric clinical trial for weight reduction, 62% of WEGOVY injection-treated patients and 42% of placebo-treated patients reported gastrointestinal adverse reactions. The most frequently reported reactions were nausea (42% vs. 18%), vomiting (36% vs. 10%), and diarrhea (22% vs. 19%). Other gastrointestinal-related reactions that occurred at a higher incidence than placebo among WEGOVY injection-treated pediatric patients included abdominal pain, constipation, eructation, gastroesophageal reflux disease, dyspepsia, and flatulence. Permanent discontinuation of treatment as a result of a gastrointestinal adverse reaction occurred in 4.3% of WEGOVY injection-treated adult patients versus 0.7% of placebo-treated patients. In a pediatric clinical trial for weight reduction, 2.3% of patients treated with WEGOVY injection versus 1.5% of patients who received placebo discontinued treatment as a result of gastrointestinal adverse reactions. Dysesthesia Dysesthesia, and related events of altered skin sensations including paresthesia, pain of skin, sensitive skin, and burning skin sensation, occurred in clinical trials with WEGOVY injection and tablet. The incidence of dysesthesia with WEGOVY increased with increasing dosage and drug levels in the blood. In clinical trials evaluating patients with and without type 2 diabetes mellitus, WEGOVY 7.2 mg injection dysesthesia was reported at a higher rate in the WEGOVY 7.2 mg injection group (22%), compared to WEGOVY 2.4 mg injection (6%) and placebo (0.3%). Among 288 patients who experienced dysesthesia with WEGOVY 7.2 mg injection, 2% permanently discontinued treatment, 8% had temporary interruption, and 23% had dose reduction; most subjects with these actions taken to WEGOVY 7.2 mg injection (permanent discontinuation, temporary interruption, or dose reduction) recovered from the event. When an action was taken with WEGOVY, events resolved faster than the events where no action was taken with WEGOVY. Among patients who experienced dysesthesia with WEGOVY 7.2 mg injection, 18% did not report recovering during the trial duration; in most of the patients who did not recover, the WEGOVY dosage was unchanged and not discontinued. Of the patients who recovered after action taken with WEGOVY, 38 patients were re-escalated to 7.2 mg. Of these 38 patients, 17 (45%) subsequently reported recurrence of dysesthesia. In a clinical trial with WEGOVY 25 mg tablets, 5% of WEGOVY-treated patients and no placebo-treated patients reported dysesthesia adverse reactions. Other Adverse Reactions in Adults and/or Pediatric Patients The below adverse reactions were reported in WEGOVY injection clinical trials and are applicable to both WEGOVY injection and WEGOVY tablets. The safety of WEGOVY tablets have not been established in pediatric patients or patients with MASH. Acute Pancreatitis In WEGOVY clinical trials in adults for weight reduction, acute pancreatitis was confirmed by adjudication in 4 WEGOVY-treated patients (0.2 cases per 100 patient years) and 1 in placebo-treated patients (less than 0.1 cases per 100 patient years). One additional case of acute pancreatitis was confirmed in a patient treated with WEGOVY in another clinical trial. Acute Kidney Injury Acute kidney injury occurred in clinical trials for weight reduction in 7 adult patients (0.4 cases per 100 patient years) receiving WEGOVY versus 4 patients (0.2 cases per 100 patient years of exposure) receiving placebo. Some of these adverse reactions occurred in association with gastrointestinal adverse reactions or dehydration. In addition, 2 patients treated with WEGOVY had acute kidney injury with dehydration in other clinical trials. The risk of renal adverse reactions with WEGOVY was increased in adult patients with a history of renal impairment (trials included 65 patients with a history of moderate or severe renal impairment at baseline), and occurred more frequently during dose titration. Increase in Heart Rate Mean increases in resting heart rate of 1 to 4 beats per minute (bpm) were observed with routine clinical monitoring in WEGOVY-treated adult patients compared to placebo in clinical trials for weight reduction. In weight reduction trials in which adult patients were randomized prior to dose-escalation, more patients treated with WEGOVY, compared with placebo, had maximum changes from baseline at any visit of 10 to 19 bpm (41% versus 34%, respectively) and 20 bpm or more (26% versus 16%, respectively). In a clinical trial for weight reduction in pediatric patients aged 12 years and older with normal baseline heart rate, more patients treated with WEGOVY compared to placebo had maximum changes in heart rate of 20 bpm or more (54% versus 39%). Hypotension and Syncope Adverse reactions related to hypotension (hypotension, orthostatic hypotension, and decreased blood pressure) were reported in 1.3% of WEGOVY-treated adult patients versus 0.4% of placebo-treated patients and syncope was reported in 0.8% of WEGOVY-treated patients versus 0.2% of placebo-treated patients in clinical trials for weight reduction. Some reactions were related to gastrointestinal adverse reactions and volume loss associated with WEGOVY. Hypotension and orthostatic hypotension were more frequently seen in patients on concomitant antihypertensive therapy. In a clinical trial in pediatric patients aged 12 years and older for weight reduction, hypotension was reported in 2.3% of WEGOVY-treated patients versus 0% in placebo-treated patients. Appendicitis Appendicitis (including perforated appendicitis) occurred in 10 (0.5%) WEGOVY-treated adult patients and 2 (0.2%) patients receiving placebo in clinical trials for weight reduction. Injection Site Reactions In clinical trials in adults for weight reduction, 1.4% of WEGOVY-treated patients and 1% of patients receiving placebo experienced injection site reactions (including injection site pruritus, erythema, inflammation, induration, and irritation). Hypersensitivity Reactions Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported with WEGOVY. In a pediatric clinical trial for weight reduction, rash was reported in 3% of WEGOVY-treated patients and 0% of placebo-treated patients, and urticaria was reported in 3% of WEGOVY-treated patients and 0% of placebo-treated patients . In adult clinical trials for weight reduction, allergic reactions occurred in 16% (8/50) of WEGOVY-treated patients with anti-semaglutide antibodies and in 7% (114/1659) of WEGOVY-treated patients who did not develop anti-semaglutide antibodies [see Clinical Pharmacology ( 12.6 )]. Fractures In the CV outcomes trial in adults, more fractures of the hip and pelvis were reported on WEGOVY than on placebo in female patients: 1% (24/2,448) vs. 0.2% (5/2,424), and in patients ages 75 years and older: 2.4% (17/703) vs. 0.6% (4/663), respectively. In a clinical trial in adults with MASH, fractures occurred in 4.4% of WEGOVY-treated patients (2.6 cases per 100 patient years) compared to 3.3% of placebo-treated patients (2 cases per 100 patient years). Fractures were reported in both males and females with a median age of 61 years (range, 44 to 75). Urolithiasis In a CV outcomes trial, 1.2% of WEGOVY-treated patients and 0.8% of patients receiving placebo reported urolithiasis, including serious reactions that were reported more frequently among patients receiving WEGOVY (0.6%) than placebo (0.4%). Dysgeusia In clinical trials in adults for weight reduction, 1.7% of WEGOVY-treated patients and 0.5% of placebo-treated patients reported dysgeusia. Hair Loss Hair loss adverse reactions in WEGOVY injection-treated patients were associated with weight reduction. In a pool of studies 2, 3, and 4, hair loss was reported in 3.3% of patients treated with WEGOVY 2.4 mg (4% female, 0.9% male) and in 1% of patients treated with placebo (2% female, 0 male). In a pediatric trial, hair loss was reported in 4% of patients treated with 2.4 mg of WEGOVY and no placebo-treated patients. In clinical trials with WEGOVY 7.2 mg injection, hair loss was reported in 5.8% of patients treated with WEGOVY 7.2 mg (8.4% female, 0.2% male), 3.3% of patients treated with WEGOVY 2.4 mg (5.4% female, 0 male), and 1.0% of patients on placebo (1.5% female, 0 male). In the WEGOVY 7.2 mg group, 1 event led to permanent treatment discontinuation, 1 event led to temporary interruption, and 5 events led to dose reduction, versus none of these actions in the WEGOVY 2.4 mg or placebo groups. Laboratory Abnormalities in Adults and/or Pediatric Patients Treated with WEGOVY Injection The below laboratory abnormalities are applicable for both WEGOVY injection and WEGOVY tablets and include descriptions of WEGOVY injection clinical trial data, where relevant. The safety and effectiveness of WEGOVY tablets have not been established in pediatric patients or patients with MASH. Amylase and Lipase Adult and pediatric patients treated with WEGOVY had a mean increase from baseline in amylase of 15% to 16% and lipase of 39% in clinical trials for weight reduction. These changes were not observed in the placebo group. In a clinical trial in adults with MASH, increases in lipase greater than 3 times the upper limit of normal (ULN) occurred in 4.7% (35/750) of WEGOVY-treated patients compared with 1.3% (5/374) of placebo-treated patients. The clinical significance of elevations in lipase or amylase with WEGOVY is unknown in the absence of other signs and symptoms of pancreatitis. Liver Tests In a pediatric clinical trial for weight reduction, increases in alanine aminotransferase (ALT) greater than or equal to 5 times the ULN were observed in 4 (3%) WEGOVY-treated patients compared with 0% of placebo-treated patients. In some patients, increases in ALT and AST were associated with other confounding factors (such as gallstones). In the CV outcomes trial in adults, increases in total bilirubin greater than or equal to 3 times the ULN were observed in 0.3% (30/8,585) of WEGOVY-treated patients versus 0.2% (14/8,579) of placebo-treated patients. 6.2 Postmarketing Experience The following adverse reactions have been reported during post-approval use of semaglutide, the active ingredient of WEGOVY. 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 Disorders: acute pancreatitis and necrotizing pancreatitis, sometimes resulting in death; ileus, intestinal obstruction, severe constipation including fecal impaction Hypersensitivity: anaphylaxis, angioedema, rash, urticaria Pulmonary: Pulmonary aspiration has occurred in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation Renal and Urinary Disorders: acute kidney injury

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.