N Engl J Med

Oral semaglutide 25 mg yields double-digit weight loss in adults with obesity

September 19, 2025

Oral semaglutide 25 mg shows promise as an effective, non-injectable option for obesity management, with weight loss efficacy comparable to injectable GLP-1 receptor agonists and higher-dose oral semaglutide (50 mg).

Study details: This 71-week, double-blind, randomized, placebo-controlled trial (OASIS 4; NCT05564117) enrolled adults without diabetes and with BMI ≥30 kg/m² or ≥27 kg/m² plus an obesity-related complication. Participants (n = 307) were randomized 2:1 to oral semaglutide 25 mg daily or placebo, both with lifestyle intervention. Coprimary endpoints were percent change in body weight and proportion achieving ≥5% weight loss at week 64; secondary endpoints included ≥10%, ≥15%, and ≥20% weight loss and change in Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function score.

Results: Oral semaglutide 25 mg resulted in a mean weight loss of 13.6% vs. 2.2% with placebo (difference, -11.4 percentage points; 95% confidence interval, -13.9 to -9.0; P<0.001). Significantly more semaglutide recipients achieved ≥5%, ≥10%, ≥15%, and ≥20% weight loss compared with placebo (all P<0.001), along with improved physical function scores. GI adverse events were more frequent with semaglutide (74% vs. 42%), but most were mild to moderate.

Source:

Wharton S, et al; OASIS 4 Study Group. (2025, September 18). N Engl J Med. Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity. https://pubmed.ncbi.nlm.nih.gov/40934115/