The US Food and Drug Administration approved once-daily oral semaglutide 25 mg (Wegovy pill) for chronic weight management and for reducing major adverse cardiovascular events in adults with overweight or obesity, marking the first oral glucagon-like peptide-1 receptor agonist authorized for weight management. The decision was supported primarily by findings from the phase 3 OASIS 4 trial and the SELECT trial, according to Novo Nordisk.
OASIS 4 was a 64-week, randomized, double-blind, placebo-controlled phase 3b study enrolling 307 adults with obesity (BMI 30 kg/m2 or greater) or overweight (BMI 27 kg/m2 or greater ) and at least one weight-related comorbidity, excluding diabetes. Participants were randomized 2:1 to oral semaglutide 25 mg once daily or placebo, alongside lifestyle intervention, following a 12-week dose-escalation period and a 7-week off-treatment follow-up. Under the trial product estimand, reflecting outcomes assuming full treatment adherence, mean body weight reduction at 64 weeks reached 16.6% with oral semaglutide compared with 2.7% with placebo. Using the treatment policy estimand, which accounted for discontinuation and rescue therapies, mean weight loss was 13.6% versus 2.4%, respectively.
One-third of participants receiving oral semaglutide achieved at least 20% weight loss, and 76% achieved a reduction of 5% or greater from baseline body weight, compared with 31% in the placebo group. Weight loss magnitude was reported to be comparable to that observed with once-weekly injectable semaglutide 2.4 mg. Adverse events were consistent with the established semaglutide safety profile, with gastrointestinal symptoms such as nausea, diarrhea, and vomiting most frequently reported.
The FDA approval also incorporated evidence from the SELECT trial demonstrating cardiovascular risk reduction with semaglutide in adults with established cardiovascular disease and overweight or obesity. Novo Nordisk reported plans to launch the oral formulation in the US in early January 2026, with regulatory submissions ongoing in Europe.
Source: Novo Nordisk, PR Newswire