FDA Approves Oral Wegovy for Weight Management

The Food and Drug Administration (FDA) has approved Wegovy® (semaglutide) tablets, the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for the treatment of obesity.

Specifically, the Wegovy tablet formulation 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; and 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 1 weight-related comorbid condition.

The approval was based on data from the randomized, double-blind, placebo-controlled phase 3 OASIS 4 trial (ClinicalTrials.gov Identifier: NCT05564117), which included 307 adults with obesity (body mass index [BMI] ≥30kg/m2) or overweight (BMI 27-29.9kg/m2) and at least 1 weight-related comorbidity, without diabetes. 

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Study participants (mean baseline body weight: 106kg; mean BMI: 38kg/m2) were randomly assigned 2:1 to receive oral semaglutide 25mg (n=205) or placebo (n=102) once daily, alongside lifestyle intervention (eg, reduced-calorie diet, increased physical activity), for 64 weeks. The coprimary endpoints were the mean percent change in body weight and the percentage of patients achieving greater than or equal to 5% weight loss from baseline to week 64. 

Findings showed semaglutide led to a -13.6% change from baseline in body weight compared with a -2.4% change in baseline with placebo (difference, -11.2 [95% CI, -13.6, -8.8]; P <.0001). Additionally, a greater proportion of patients receiving semaglutide achieved at least a 5% body weight reduction vs placebo (76.3% vs 31.3%; difference, 45.1 [95% CI, 33.8-56.3]; P <.0001). 

Results also showed significantly more patients (all P <.0001) in the semaglutide arm vs placebo arm achieved a weight loss of at least 10% (difference, 45.3% [95% CI, 35.5-55.2]), at least 15% (difference, 41.5% [95% CI, 33.2-49.8]), and at least 20% (difference, 24.8% [95% CI, 17.7-31.9]). 

Notably, semaglutide-treated patients also saw improvements in cardiometabolic risk factors (eg, waist circumference, blood pressure, low density lipoprotein cholesterol, triglycerides) as well.

The most common adverse reactions reported with treatment were nausea, vomiting and diarrhea. The prescribing information also includes a boxed warning regarding the risk of thyroid C-cell tumors. 

“With Wegovy pill, we are offering a magnitude of weight loss that no other oral GLP-1 obesity candidate has been able to duplicate in phase 3 trials,” said Dave Moore, executive vice president, US Operations at Novo Nordisk. “We are confident that the expansion of Wegovy to a pill will help patients who may have not sought or accepted treatment before.”

Wegovy tablets are supplied in strengths of 1.5mg, 4mg, 9mg, and 25mg. It is expected to be available in early January 2026.