Wegovy (semaglutide): NDA 218316

Other approved indications include the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) (accelerated approval; Wegovy) and to reduce the risk of sustained eGFR decline, end-stage kidney disease and CV death in adults with T2D and chronic kidney disease (Ozempic).

The Office of Pharmaceutical Quality recommended approval across all review disciplines, including drug product assessment, manufacturing, biopharmaceutics, and labeling.

Wegovy is also approved for CV risk reduction, and has accelerated approval for MASH.

Substantial evidence of effectiveness for the semaglutide 25 mg tablet for long-term weight reduction in overweight and obesity was established with one adequate and well-controlled investigation (OASIS 4) with confirmatory evidence.

OASIS 4 demonstrated clinically meaningful and statistically significant weight loss (-11.28% treatment difference vs. placebo, 95% CI: -13.68, -8.88) with 76.7% of patients achieving >=5% weight loss compared to 31.9% with placebo.

In adults, body mass index (BMI) is commonly used to identify individuals with obesity or overweight, using cut-offs generally selected based on epidemiological data demonstrating a positive relationship to cardiovascular (CV) morbidity and mortality with increasing BMI.

Serious adverse events were not reported to a greater extent in semaglutide 25 mg vs. placebo subjects in OASIS 4. The safety of semaglutide 25 mg tablet was further supported by 2 trials evaluating semaglutide 50 mg PO for long-term weight reduction.

The application provides substantial evidence of effectiveness based on one adequate and wellcontrolled investigation (OASIS 4) with confirmatory evidence from the STEP program bridged through exposure-response analyses.

The weight management indication is supported by clinically meaningful and statistically significant weight loss that is comparable to the approved subcutaneous formulation.

Conduct a medullary thyroid carcinoma registry-based case series of at least 15 years duration to systematically monitor the annual incidence of medullary thyroid carcinoma in the United States and to identify any increase related to the introduction of semaglutide tablet for the treatment of obesity into the marketplace.

As seen in Table 85, cholelithiasis was the only serious and severe preferred term that was reported in more than 1 subject.

Most common adverse reactions (incidence >=5%) in adults or pediatric patients aged 12 years and older are: nausea, diarrhea, vomiting, constipation, abdominal pain, dysesthesia, headache, fatigue, dyspepsia, dizziness, abdominal distension, eructation, hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis, gastroesophageal reflux disease, and hair loss.

Cholecystitis was reported by 0.8% of WEGOVY injection-treated pediatric patients and 0% placebo-treated patients [see Adverse Reactions (6.1)].

Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in WEGOVY-treated patients than in placebo-treated patients, even after accounting for the degree of weight loss.

In glycemic control clinical trials, the risk of hypoglycemia was increased when semaglutide injection or tablet was used concomitantly with insulin or an insulin secretagogue (e.g., sulfonylurea).

A PMR communication letter to conduct extrapolation analyses for long-term weight reduction in pediatric patients 6 years and above was issued on November 21 2025; Reference ID: 5700136.