SEMAGLUTIDE: 59,604 Adverse Event Reports & Safety Profile

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 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. 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: Salcaprozate sodium (SNAC) and magnesium stearate. structural-formula

AND USAGE 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 [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. ( 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 )

AND ADMINISTRATION 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

2.1 Important Monitoring and Administration Instructions In patients with diabetes mellitus, monitor blood glucose prior to starting WEGOVY and during WEGOVY treatment <span class="opacity-50 text-xs">[see Warnings and Precautions (5.4 )]</span> . Administer WEGOVY in combination with a reduced-calorie diet and increased physical activity.

Wegovy

Injection

• Prior to initiation of WEGOVY injection, train patients on proper injection technique. Refer to the accompanying Instructions for Use for complete administration instructions with illustrations.
• Visually inspect the WEGOVY injection prior to each administration. Only use if 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.

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 )] .
• Do not take more than one tablet per day.
• Swallow tablets whole. Do not split, crush, chew or dissolve in any solution.
• 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 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 and Pediatric Patients Aged 12 Years and Older The maintenance dosage of WEGOVY injection for weight reduction in adults and 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 ( 14.2 , 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 )] .
• Do not take more than one tablet per day.

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, resume dosing as scheduled or, if needed, reinitiate WEGOVY injection and follow the dosage escalation schedule, which may reduce the occurrence of gastrointestinal adverse reactions associated with reinitiation of treatment [see Dosage and Administration ( 2.2 )].

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 ), and Clinical Pharmacology ( 12.3 )].

RYBELSUS and OZEMPIC tablets are contraindicated in patients with:

• A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Warnings and Precautions ( 5.1 )] .
• A prior serious hypersensitivity reaction to semaglutide or to any of the excipients in RYBELSUS or OZEMPIC tablets. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with semaglutide tablets [see Warnings and Precautions ( 5.7 )] .
• Personal or family history of MTC or in patients with MEN 2 syndrome type 2 ( 4 )
• Prior serious hypersensitivity reaction to semaglutide or any of the excipients in OZEMPIC ( 4 )

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 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 )]
• Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.10 )]
• Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions ( 5.11 )] 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 for Weight Reduction 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 CV 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 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 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

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 tablet 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, 75.6% were female, 92.7% were White, 0.5% were Asian, 6.3% were Black or African American, and 8.3% 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 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 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

4 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 study in pediatric patients aged 12 years and older.

Table

4.

Adverse

Reactions (≥3% and Greater than Placebo) in WEGOVY 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 9) 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 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 dose and the 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.

Other Adverse

Reactions in Adults and/or Pediatric Patients Treated with WEGOVY Injection The below adverse reactions 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.

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.

Other Adverse

Reactions in Adult Patients Treated with WEGOVY Tablets for Weight Reduction Dysesthesia In a clinical trial with WEGOVY tablets, 4.9% of WEGOVY-treated patients and no placebo-treated patients reported dysesthesia adverse reactions, with preferred terms including sensitive skin, hyperesthesia, paresthesia, allodynia, and skin burning sensation.

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

AND PRECAUTIONS

• Acute Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, including semaglutide. Discontinue if pancreatitis is suspected. ( 5.2 )
• Diabetic Retinopathy Complications: Has been reported in a clinical trial. Patients with a history of diabetic retinopathy should be monitored. ( 5.3 )
• Never share an OZEMPIC pen between patients , even if the needle is changed. ( 5.4 )
• Hypoglycemia: Concomitant use with an insulin secretagogue or insulin may increase the risk of hypoglycemia, including severe hypoglycemia. Reducing dose of insulin secretagogue or insulin may be necessary. ( 5.5 )
• Acute Kidney Injury Due to Volume Depletion: Monitor renal function in patients reporting adverse reactions that could lead to volume depletion. ( 5.6 )
• Severe Gastrointestinal Adverse Reactions : Use has been associated with gastrointestinal adverse reactions, sometimes severe. OZEMPIC is not recommended in patients with severe gastroparesis. ( 5.7 )
• Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis and angioedema) have been reported. Discontinue OZEMPIC if suspected and promptly seek medical advice. ( 5.8 )
• Acute Gallbladder Disease: If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated. ( 5.9 )
• Pulmonary Aspiration During General Anesthesia or Deep Sedation: Has been reported in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures. Instruct patients to inform healthcare providers of any planned surgeries or procedures. ( 5.10 )

5.1 Risk of Thyroid C-Cell Tumors In mice and rats, semaglutide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure at clinically relevant plasma exposures <span class="opacity-50 text-xs">[see Nonclinical Toxicology ( 13.1 )]</span> . It is unknown whether OZEMPIC causes thyroid C-cell tumors, including MTC, in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined. Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist use in humans. OZEMPIC is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of OZEMPIC and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with OZEMPIC. Such monitoring may increase the risk of unnecessary procedures, due to the low-test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin value may indicate MTC and patients with MTC usually have calcitonin values &gt;50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.

5.2 Acute Pancreatitis Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including semaglutide <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span>. After initiation of OZEMPIC, observe patients carefully for signs and symptoms of acute pancreatitis which may include persistent or severe abdominal pain (sometimes radiating to the back) and which may or may not be accompanied by nausea or vomiting. If pancreatitis is suspected, discontinue OZEMPIC and initiate appropriate management.

5.3 Diabetic Retinopathy Complications In a 2-year trial involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with OZEMPIC (3.0%) 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 (OZEMPIC 8.2%, placebo 5.2%) than among patients without a known history of diabetic retinopathy (OZEMPIC 0.7%, placebo 0.4%). Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. The effect of long-term glycemic control with semaglutide on diabetic retinopathy complications has not been studied. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy.

5.4 Never Share an OZEMPIC Pen Between Patients OZEMPIC pens must never be shared between patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens.

5.5 Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin Patients receiving OZEMPIC in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 ), Drug Interactions ( 7 )]</span>. The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.

5.6 Acute Kidney Injury Due to Volume Depletion There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with semaglutide. The majority of the reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span>. Monitor renal function in patients reporting adverse reactions to OZEMPIC that could lead to volume depletion, especially during dosage initiation and escalation of OZEMPIC.

5.7 Severe Gastrointestinal Adverse Reactions Use of OZEMPIC has been associated with gastrointestinal adverse reactions, sometimes severe <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 )]</span>. In OZEMPIC clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving OZEMPIC (0.5 mg 0.4%, 1 mg 0.8%) than placebo (0%). Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists. OZEMPIC is not recommended in patients with severe gastroparesis.

5.8 Hypersensitivity Reactions Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with OZEMPIC. If hypersensitivity reactions occur, discontinue use of OZEMPIC; treat promptly per standard of care, and monitor until signs and symptoms resolve. Do not use in patients with a previous hypersensitivity to OZEMPIC <span class="opacity-50 text-xs">[see Contraindications ( 4 ), Adverse Reactions ( 6.2 )]</span> . Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to anaphylaxis with OZEMPIC.

5.9 Acute Gallbladder Disease Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In placebo-controlled trials, cholelithiasis was reported in 1.5% and 0.4% of patients-treated with OZEMPIC 0.5 mg and 1 mg, respectively. Cholelithiasis was not reported in placebo-treated patients. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.

5.10 Pulmonary Aspiration During General Anesthesia or Deep Sedation OZEMPIC delays gastric emptying <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.2 ) ]</span>. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking OZEMPIC, including whether modifying preoperative fasting recommendations or temporarily discontinuing OZEMPIC could reduce the incidence of retained gastric contents. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking OZEMPIC.

5.1 Risk of Thyroid C-Cell Tumors In mice and rats, semaglutide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure at clinically relevant plasma exposures <span class="opacity-50 text-xs">[see Nonclinical Toxicology ( 13.1 )]</span> . It is unknown whether OZEMPIC causes thyroid C-cell tumors, including MTC, in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined. Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist use in humans. OZEMPIC is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of OZEMPIC and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with OZEMPIC. Such monitoring may increase the risk of unnecessary procedures, due to the low-test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin value may indicate MTC and patients with MTC usually have calcitonin values &gt;50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.

5.2 Acute Pancreatitis Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including semaglutide <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span>. After initiation of OZEMPIC, observe patients carefully for signs and symptoms of acute pancreatitis which may include persistent or severe abdominal pain (sometimes radiating to the back) and which may or may not be accompanied by nausea or vomiting. If pancreatitis is suspected, discontinue OZEMPIC and initiate appropriate management.

5.3 Diabetic Retinopathy Complications In a 2-year trial involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with OZEMPIC (3.0%) 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 (OZEMPIC 8.2%, placebo 5.2%) than among patients without a known history of diabetic retinopathy (OZEMPIC 0.7%, placebo 0.4%). Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. The effect of long-term glycemic control with semaglutide on diabetic retinopathy complications has not been studied. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy.

5.4 Never Share an OZEMPIC Pen Between Patients OZEMPIC pens must never be shared between patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens.

5.5 Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin Patients receiving OZEMPIC in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 ), Drug Interactions ( 7 )]</span>. The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.

5.6 Acute Kidney Injury Due to Volume Depletion There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with semaglutide. The majority of the reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span>. Monitor renal function in patients reporting adverse reactions to OZEMPIC that could lead to volume depletion, especially during dosage initiation and escalation of OZEMPIC.

5.8 Hypersensitivity Reactions Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with OZEMPIC. If hypersensitivity reactions occur, discontinue use of OZEMPIC; treat promptly per standard of care, and monitor until signs and symptoms resolve. Do not use in patients with a previous hypersensitivity to OZEMPIC <span class="opacity-50 text-xs">[see Contraindications ( 4 ), Adverse Reactions ( 6.2 )]</span> . Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to anaphylaxis with OZEMPIC.

INTERACTIONS Oral Medications : OZEMPIC delays gastric emptying. May impact absorption of concomitantly administered oral medications. Use with caution ( 7.2 ).

7.1 Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin OZEMPIC stimulates insulin release in the presence of elevated blood glucose concentrations. Patients receiving OZEMPIC in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. When initiating OZEMPIC, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.5 ) and Adverse Reactions ( 6 )]</span> .

7.2 Oral Medications OZEMPIC causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, semaglutide did not affect the absorption of orally administered medications to any clinically relevant degree <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> . Nonetheless, caution should be exercised when oral medications are concomitantly administered with OZEMPIC.

7.1 Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin OZEMPIC stimulates insulin release in the presence of elevated blood glucose concentrations. Patients receiving OZEMPIC in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. When initiating OZEMPIC, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.5 ) and Adverse Reactions ( 6 )]</span> .

7.2 Oral Medications OZEMPIC causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, semaglutide did not affect the absorption of orally administered medications to any clinically relevant degree <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> . Nonetheless, caution should be exercised when oral medications are concomitantly administered with OZEMPIC.