Oral Semaglutide 25 mg Produces 13.6% Weight Loss in People with Obesity (OASIS 4 Trial)

OASIS 4 was a 71-week, double-blind, randomized, placebo-controlled trial conducted at 22 sites across four countries. 307 participants without diabetes who had a BMI ≥30 (or ≥27 with at least one obesity-related complication) were randomized 2:1 to oral semaglutide 25 mg or placebo once daily, alongside lifestyle interventions. Coprimary endpoints at week 64 were percent change in body weight and achieving ≥5% weight loss.

Injectable semaglutide (Wegovy) is already a blockbuster weight loss drug, but many patients prefer pills to injections. This trial shows a 25 mg oral dose — lower than the 50 mg also being studied — can produce clinically significant weight loss of nearly 14%. This dose could offer a middle ground: more weight loss than the current 14 mg oral dose (approved for diabetes as Rybelsus) while being more practical than injections for patients who prefer oral medication.

The OASIS trial program is systematically testing oral semaglutide at higher doses than currently approved. While injectable semaglutide 2.4 mg (Wegovy) produces about 15% weight loss, oral semaglutide 25 mg achieves 13.6% — closing the gap between pill and injection. This matters enormously for market access, patient preference, and global obesity treatment, especially in populations where self-injection is a barrier to treatment.

The sample size (307 participants) is modest for a phase 3 weight loss trial. People with diabetes were excluded, limiting generalizability. The 74% gastrointestinal adverse event rate is high, though described as predominantly transient. The trial was funded by Novo Nordisk, the manufacturer. No head-to-head comparison with injectable semaglutide was performed in this trial.