Wegovy (Semaglutide)

• •
  In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether WEGOVY causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined

  [see Warnings and Precautions (

  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

  [see Nonclinical Toxicology (

  13.1

  )]

  . It is unknown whether WEGOVY 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.

  WEGOVY 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 WEGOVY 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 WEGOVY. 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 greater than 50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.

  ), Nonclinical Toxicology (

  13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

  In a 2-year carcinogenicity study in CD-1 mice, subcutaneous doses of 0.3, 1 and 3 mg/kg/day (2-, 8-, and 22-fold the maximum recommended human dose [MRHD] of WEGOVY subcutaneous injection 2.4 mg/week, or WEGOVY oral tablet 25 mg daily based on AUC) were administered to the males, and 0.1, 0.3 and 1 mg/kg/day (0.6-, 2-, and 5-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 (greater than or equal to 0.6 times human exposure).

  In a 2-year carcinogenicity study in Sprague Dawley rats, subcutaneous doses of 0.0025, 0.01, 0.025 and 0.1 mg/kg/day were administered (below quantification, 0.2-, 0.4-, and 2-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 Boxed Warning, Warnings and Precautions ]

  . Semaglutide was not mutagenic or clastogenic in a standard battery of genotoxicity tests (bacterial mutagenicity [Ames] human lymphocyte chromosome aberration, rat bone marrow micronucleus).

  In a combined fertility and embryo-fetal development study in rats, subcutaneous doses of 0.01, 0.03 and 0.09 mg/kg/day (0.04-, 0.1-, and 0.4-fold the MRHD) were administered to 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. These effects were likely an adaptive response secondary to the pharmacological effect of semaglutide on food consumption and body weight.

  )]

  .
• •
  WEGOVY is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)

  [see Contraindications (

  4 CONTRAINDICATIONS

  WEGOVY is contraindicated in the following conditions:

  • •A personal or family history of MTC or in patients with MEN 2
    [see Warnings and Precautions (

    5.1

    )]
    .
  • •A prior serious hypersensitivity reaction to semaglutide or to any of the excipients in WEGOVY injection or WEGOVY tablet. Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with WEGOVY
    [see Warnings and Precautions ]
    .

  • •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
    )

  )]

  . Counsel patients regarding the potential risk for MTC with the use of WEGOVY 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 WEGOVY

  [see Contraindications (

  4 CONTRAINDICATIONS

  WEGOVY is contraindicated in the following conditions:

  • •A personal or family history of MTC or in patients with MEN 2
    [see Warnings and Precautions (

    5.1

    )]
    .
  • •A prior serious hypersensitivity reaction to semaglutide or to any of the excipients in WEGOVY injection or WEGOVY tablet. Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with WEGOVY
    [see Warnings and Precautions ]
    .

  • •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
    )

  ), Warnings and Precautions (

  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

  [see Nonclinical Toxicology (

  13.1

  )]

  . It is unknown whether WEGOVY 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.

  WEGOVY 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 WEGOVY 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 WEGOVY. 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 greater than 50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.

  )]

  .

Indications and Usage (

Dosage and Administration (

Warnings and Precautions,

•  Acute Kidney Injury Due to Volume Depletion (
  5.5 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

  [see Adverse Reactions (

  6)]

  . The majority of the reported events occurred in patients who experienced gastrointestinal adverse reactions leading to dehydration such as nausea, vomiting, or diarrhea

  [see Adverse Reactions ]

  .

  Monitor renal function in patients reporting adverse reactions to WEGOVY that could lead to volume depletion, especially during dosage initiation and escalation of WEGOVY.
  )..………….08/2025
•  Severe Gastrointestinal Adverse Reactions (
  5.6 Severe Gastrointestinal Adverse Reactions

  Use of WEGOVY has been associated with gastrointestinal adverse reactions, sometimes severe

  [see Adverse Reactions ]

  . In clinical trials for adults for weight reduction, severe gastrointestinal adverse reactions were reported more frequently among patients receiving WEGOVY than placebo. Severe gastrointestinal adverse reactions were reported in 4.1% and 0.9% of WEGOVY-injection and placebo-treated patients, respectively, and in 2% of WEGOVY tablet-treated and 0% of placebo-treated patients, respectively. Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists.

  WEGOVY is not recommended in patients with severe gastroparesis.
  )………………..10/2025

• •
  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 Noncirrhotic Metabolic Dysfunction-associated Steatohepatitis with Moderate to Advanced Liver Fibrosis in Adults Treated with WEGOVY Injection

  Overview of Clinical Trial

  The efficacy of WEGOVY injection was evaluated based on an efficacy analysis at Week 72 in Study 9 (NCT#04822181), a 240-week, randomized, double-blind, placebo-controlled trial. Enrolled patients had a baseline or recent liver biopsy showing clinically significant MASLD (metabolic dysfunction-associated steatotic liver disease), defined as MASH with fibrosis stage 2 or 3 and a non-alcoholic fatty liver disease (NAFLD) Activity Score (NAS) ≥4 with a score of 1 or more in steatosis, lobular inflammation, and hepatocyte ballooning. Efficacy determination was based on the effect of WEGOVY injection on resolution of steatohepatitis without worsening of liver fibrosis and on at least one stage improvement in liver fibrosis without worsening of steatohepatitis, on post-baseline liver biopsies collected at 72 weeks.

  The Week 72 analysis included 800 F2 and F3 (at eligibility) patients randomized 1:2 to receive placebo (n=266) or WEGOVY once weekly (n=534), in addition to standard of care for cardiometabolic comorbidities and healthy lifestyle counseling. WEGOVY injection or matching placebo was escalated to 2.4 mg once weekly during the initial 16 weeks of the treatment period. Dose escalation could be prolonged or patients could remain at a lower dose if 2.4 mg once weekly was not tolerable.

  Demographic and baseline characteristics were balanced between treatment and placebo groups. Overall, the median (Q1 to Q3) age of patients at baseline was 57 (49 to 65) years, 57% were female, 18% were Hispanic, 68% were White, 27% were Asian, and 0.6% were Black or African American. Median (Q1 to Q3) body mass index (BMI) was 34 (30 to 38) kg/m²and median (Q1 to Q3) body weight was 93 (79 to 110) kg. Baseline characteristics are presented in

  Table 17

  .

  Table 17. Baseline Characteristics in Adults Patients with Noncirrhotic MASH with Stage 2 to Stage 3 Fibrosis in Study 9

  Characteristic	Overall (N=800)
  Fibrosis stage, n (%) F2 F3	250 (31) 550 (69)
  Body Mass Index (BMI, kg/m2), n (%)a <25 25-30 30-35 ≥35	53 (7) 164 (21) 252 (32) 330 (41)
  Lean MASH, n (%)b	22 (3)
  Type 2 Diabetes, n (%)	447 (56)
  Hypertension, n (%)	503 (63)
  Dyslipidemia, n (%)	198 (25)
  Statin use, n (%)	300 (38)
  Fibrosis Index Based on 4 Factors (FIB-4), Median (Q1, Q3)a	1.6 (1.1, 2.3)
  Enhanced Liver Fibrosis (ELF), Median (Q1, Q3)	9.9 (9.3, 10.5)

  ^aLess than 5% missingness in the variable is omitted.

  ^bLean MASH defined as BMI <25 kg/m²for non-Asian patients and BMI <23 kg/m²for Asian patients.

  Among the 79% of the patients with vibration-controlled transient elastography (VCTE) at baseline, median (Q1 to Q3) VCTE was 10.9 (8.6 to 15.5) kPa, which may not be representative of the entire study population. The 21% of patients with missing VCTE at baseline had higher percentages of being female and having baseline diabetes, hypertension, and dyslipidemia.

  Results

  Table 18

  presents the Week 72 histopathology primary endpoint results comparing WEGOVY injection with placebo on

  1) the estimated percentage of patients with resolution of steatohepatitis and no worsening of liver fibrosis and
  
  2) the estimated percentage of patients with at least one stage improvement in liver fibrosis and no worsening of steatohepatitis. The secondary endpoint results of the estimated percentage of patients with resolution of steatohepatitis and improvement in liver fibrosis at Week 72 are also presented. Two pathologists independently read the liver biopsies for each patient; a third pathologist performed adjudication if consensus could not be reached between the two pathologists. WEGOVY injection demonstrated improvement on these histopathology endpoints at Week 72 compared to placebo.

  Table 18. Efficacy Results at Week 72 in Adult Patients with Noncirrhotic MASH with Stage 2 or

  Stage 3 Fibrosis in Study 9 of WEGOVY Injection

  	Placebo N=266	WEGOVY Injection N=534
  Resolution of steatohepatitis and no worsening of liver fibrosis
  Response Rate (%)	34	63
  Difference in response rate vs. placebo (95% CI)		29 (21, 36)*
  Improvement in liver fibrosis and no worsening of steatohepatitis
  Response Rate (%)	22	37
  Difference in response rate vs. placebo (95% CI)		14 (8, 21)*
  Resolution of steatohepatitis and improvement in liver fibrosis
  Response Rate (%)	16	33
  Difference in response rate vs. placebo (95% CI)		17 (10, 23)*

  ^*Results were statistically significant.

  Endpoints were evaluated according to the MASH Clinical Research Network (CRN). Resolution of steatohepatitis is defined as a score of 0 to 1 for lobular inflammation, 0 for ballooning, and any value for steatosis. No worsening of steatohepatitis is defined as no increase from baseline in score for ballooning, lobular inflammation, or steatosis.

  Estimated using pooled Mantel-Haenszel (MH) estimates stratified by baseline type 2 diabetes status (presence or absence) and baseline fibrosis stage (F2 or F3) with missing data handled by reference-based multiple imputation and 95% confidence intervals (CIs) calculated using Rubin’s rule to pool Sato’s estimate of standard errors across the imputed datasets.

  Another secondary endpoint was the percent change in body weight from baseline to Week 72. Patients treated with WEGOVY injection (mean baseline body weight 95.4 kg) achieved an average of 10.5% weight loss from baseline at Week 72, and patients treated with placebo (mean baseline weight 97.6 kg) achieved an average of 2% weight loss from baseline at Week 72; treatment with WEGOVY injection resulted in an average of 8.5% greater weight loss from baseline compared to placebo (95% CI: 7.4% to 9.5%).

  Starting at Week 12 and through Week 72, there was a trend of greater reductions from baseline in average ALT and AST in the WEGOVY injection group as compared to the placebo group.

  )]

  . Continued approval for this indication may be contingent upon the verification and description of clinical benefit in a confirmatory trial.

• •
  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.

In patients with diabetes, monitor blood glucose prior to starting and during WEGOVY treatment. (

• •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 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

  • •
    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 ]

    .
  • •
    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 ]

    .
  )
• •Inject subcutaneously in the abdomen, thigh, or upper arm. (
  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

  • •
    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 ]

    .
  • •
    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 ]

    .
  )
• •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 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 , Adverse Reactions ]

    .
  • •
    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 , Clinical Studies ]

    .

  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 , Clinical Studies ]

  .

  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 , Clinical Studies ]

  .
  )
• •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 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 , Adverse Reactions ]

    .
  • •
    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 , Clinical Studies ]

    .

  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 , Clinical Studies ]

  .

  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 , Clinical Studies ]

  .
  )

• •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 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

  • •
    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 ]

    .
  • •
    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 ]

    .
  ).
• •Swallow tablets whole. Do not split, crush, chew or dissolve. (
  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

  • •
    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 ]

    .
  • •
    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 ]

    .
  )
• •After taking WEGOVY tablet wait at least 30 minutes before eating food, drinking beverages or taking other oral medications. (
  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

  • •
    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 ]

    .
  • •
    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 ]

    .
  )
• •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 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 , Adverse Reactions ]

    .
  • •
    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 , Clinical Studies ]

    .

  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 , Clinical Studies ]

  .

  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 , Clinical Studies ]

  .
  )
• •The recommended maintenance dosage of WEGOVY tablets is 25 mg orally once daily for cardiovascular risk reduction and weight reduction in adults

Injection: clear, colorless solution available in 5 prefilled, disposable, single-dose pens:

• •0.25 mg/0.5 mL
• •0.5 mg/0.5 mL
• •1 mg/0.5 mL
• •1.7 mg/0.75 mL
• •2.4 mg/0.75 mL

Tablet: white to light yellow, round shaped debossed with the strength on one side and “novo” on the other side:

• •1.5 mg
• •4 mg
• •9 mg

Tablet: white to light yellow, oval shaped debossed with the strength on one side and “novo” on the other side:

• •25 mg

• •
  Pregnancy
  : May cause fetal harm. For patients receiving WEGOVY for CV risk reduction or weight reduction, discontinue WEGOVY when pregnancy is recognized. For patients with MASH, use during pregnancy only if the potential benefit justifies the potential risk to the fetus. (
  8.1 Pregnancy

  Pregnancy Exposure Registry

  There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to semaglutide during pregnancy. Pregnant women exposed to WEGOVY and healthcare providers are encouraged to contact Novo Nordisk at 1-877-390-2760 or www.wegovypregnancyregistry.com.

  Risk Summary

  Based on animal reproduction studies, there may be potential risks to the fetus from exposure to semaglutide during pregnancy. 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, and discontinue WEGOVY (see

  Clinical Considerations

  ).

  There may be risks to the mother and fetus related to underlying MASH with advanced liver fibrosis (see

  Clinical Considerations

  ). Whether semaglutide treatment during pregnancy reduces these risks is unknown. WEGOVY for the treatment of MASH 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 maternal exposures below the maximum recommended human dose (MRHD) based on AUC. In rabbits and cynomolgus monkeys administered semaglutide during organogenesis, early pregnancy losses and structural abnormalities were observed at below the MRHD (rabbit) and greater than or equal to 2-fold the MRHD (monkey). These findings coincided with a marked maternal body weight loss in both animal species (see

  Data

  ).

  The 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 semaglutide on these risks is unknown.

  Data

  Animal Data

  In a combined fertility and embryofetal development study in rats, subcutaneous doses of 0.01, 0.03, and 0.09 mg/kg/day (0.04-, 0.1-, and 0.4-fold the MRHD) were administered to males for 4 weeks prior to and throughout mating and to females for 2 weeks prior to mating, and throughout organogenesis to Gestation Day 17. In parental animals, pharmacologically mediated reductions in body weight gain and food consumption were observed at all dose levels. In the offspring, reduced growth and fetuses with visceral (heart blood vessels) and skeletal (cranial bones, vertebra, ribs) abnormalities were observed at the human exposure.

  In an embryofetal development study in pregnant rabbits, subcutaneous doses of 0.001, 0.0025, or 0.0075 mg/kg/day (0.01-, 0.1-, and 0.9-fold the MRHD) were administered throughout organogenesis from Gestation Day 6 to 19. Pharmacologically mediated reductions in maternal body weight gain and food consumption were observed at all dose levels. Early pregnancy losses and increased incidences of minor visceral (kidney, liver) and skeletal (sternebra) fetal abnormalities were observed at greater than or equal to 0.0025 mg/kg/day, at clinically relevant exposures.

  In an embryofetal development study in pregnant cynomolgus monkeys, subcutaneous doses of 0.015, 0.075, and 0.15 mg/kg twice weekly (0.4-, 2-, and 6-fold the MRHD) were administered throughout organogenesis, from Gestation Day 16 to 50. Pharmacologically mediated, marked initial maternal body weight loss and reductions in body weight gain and food consumption coincided with the occurrence of sporadic abnormalities (vertebra, sternebra, ribs) at greater than or equal to 0.075 mg/kg twice weekly (greater than or equal to 2 times human exposure).

  In a pre- and postnatal development study in pregnant cynomolgus monkeys, subcutaneous doses of 0.015, 0.075, and 0.15 mg/kg twice weekly (0.2-, 1-, and 3-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 (greater than or equal to 1-time human exposure).

  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.
  )
• •
  Lactation
  : Breastfeeding not recommended during treatment with WEGOVY tablets. (
  8.2 Lactation

  Risk Summary

  WEGOVY Oral Tablets

  Data from a clinical lactation study with semaglutide oral tablet formulation reported semaglutide concentrations below the lower limit of quantification in human milk. However, SNAC and/or its metabolites are present in human milk. Since the activity of enzymes involved in SNAC clearance may be lower in infants compared to adults, higher SNAC plasma levels may occur in neonates and infants. Because of the unknown potential for serious adverse reactions in the breastfed infant due to the possible accumulation of SNAC, and because there are alternative formulations of semaglutide that do not contain SNAC that can be used during lactation, advise patients that breastfeeding is not recommended during treatment with WEGOVY tablets.

  WEGOVY Subcutaneous Injection

  There are no data on the presence of subcutaneously administered semaglutide or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. WEGOVY subcutaneous injection does not contain the SNAC metabolites.

  The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for WEGOVY and any potential adverse effects on the breastfed infant from WEGOVY or from the underlying maternal condition.
  )
• •
  Females and Males of Reproductive Potential
  : For patients receiving WEGOVY for CV risk reduction or weight reduction, or for MASH where the potential risk outweighs the potential benefit, discontinue WEGOVY at least 2 months before a planned pregnancy because of the long half-life of semaglutide. (
  8.3 Females and Males of Reproductive Potential

  Because of the potential for fetal harm, discontinue WEGOVY in patients at least 2 months before they plan to become pregnant to account for the long half-life of semaglutide

  [see Use in Specific Populations ]

  .
  )