A once-daily 25 mg oral form of semaglutide produced substantial weight loss in adults with obesity in a phase 3 study published in The New England Journal of Medicine, with a 16.6% mean reduction under an adherence-based analysis and 13.6% in the overall analysis. The results were accompanied by improvements in cardiometabolic risk factors and self-reported physical function. Novo Nordisk has submitted the therapy for U.S. approval and says U.S. manufacturing is underway; the FDA is slated to decide in the fourth quarter of 2025.
Key findings
- The OASIS 4 phase 3 trial enrolled 307 adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) plus at least one weight‑related comorbidity; people with diabetes were excluded. Participants were randomized 2:1 to oral semaglutide 25 mg or placebo, alongside lifestyle counseling. The study included 64 weeks of on‑treatment follow‑up (with a 12‑week dose escalation) and a 7‑week off‑treatment follow‑up, for 71 weeks total. (NEJM; American College of Cardiology summary)
Weight loss: Mean change at week 64 was −13.6% with oral semaglutide versus −2.2% with placebo in the overall (treatment‑policy) analysis. Under the adherence-based “trial product estimand,” mean loss was −16.6% versus −2.7%. The share achieving ≥20% weight loss was 29.7% vs 3.3% in the overall analysis and 34.4% vs 2.9% in the adherence-based analysis. (NEJM; Novo Nordisk press materials; ACC summary)
Function and risk factors: Participants on oral semaglutide had greater improvements in self‑reported physical function (IWQOL‑Lite‑CT) and favorable changes in cardiometabolic risk markers (e.g., lipids, C‑reactive protein) compared with placebo. (NEJM; ACC; company analyses)
Safety: Adverse events were consistent with the GLP‑1 class and largely gastrointestinal. In OASIS 4, nausea occurred in 46.6% on semaglutide vs 18.6% on placebo; vomiting in 30.9% vs 5.9%. Discontinuations due to adverse events were 6.9% vs 5.9%, and serious adverse events occurred in 3.9% vs 8.8%, respectively. (Novo Nordisk press materials; NEJM/ACC for overall GI event rates)
How it compares
- The magnitude of weight loss with oral semaglutide 25 mg was comparable to prior results reported for injectable semaglutide 2.4 mg and for higher‑dose oral semaglutide in earlier trials, according to NEJM and a summary by the American College of Cardiology.
Regulatory status and manufacturing
- Novo Nordisk filed a U.S. application for the once‑daily Wegovy pill in February 2025; the FDA accepted the filing and, according to Reuters, plans a decision in the fourth quarter of 2025. Novo Nordisk says the pill would be fully manufactured in the United States and that production is already underway at expanded U.S. facilities. If cleared, it would be the first oral GLP‑1 therapy approved for chronic weight management. (Reuters; Novo Nordisk)
Context
- No oral GLP‑1 therapy is currently approved in the U.S. for weight management. Injectable semaglutide (Wegovy) is approved in the U.S. and European Union for weight management in adults and certain adolescents; in the U.S. it also carries an indication to reduce the risk of major adverse cardiovascular events in adults with established cardiovascular disease. (Reuters; EMA/US labels)
Quoted remarks
- “The oral semaglutide 25 mg data show compelling efficacy for an oral weight management medication with 16.6% weight loss and a safety and tolerability profile consistent with injectable Wegovy,” said Martin Holst Lange, Novo Nordisk’s chief scientific officer. “Pending FDA approval, ample supply will be available to meet the expected U.S. demand.” (Novo Nordisk)
- Lead author Sean Wharton said the results “represent a significant advancement in obesity treatment,” noting the potential for an oral option to expand patient access. (Novo Nordisk)
