The New England journal of medicineSep 11, 2025

Effects of 25 mg Oral Semaglutide in Adults with Overweight or Obesity

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 28, 2026

Abstract

Essence

In adults with overweight or obesity without diabetes, oral semaglutide 25 mg reduced body weight more than placebo by week 64.

Evidence

A 71-week double-blind randomized placebo-controlled trial at 22 sites in four countries found an estimated mean body-weight change of -13.6% with oral semaglutide versus -2.2% with placebo in 205 versus 102 participants, with more participants reaching 5%, 10%, 15%, and 20% weight-loss thresholds and improved IWQOL-Lite-CT Physical Function scores.

Caveat

The trial was relatively small and gastrointestinal adverse events were more common with oral semaglutide than placebo (74.0% vs 42.2%).

Simplified

BACKGROUND: Oral semaglutide at a dose of 25 mg may provide an alternative treatment option to injectable semaglutide (2.4 mg) and higher-dose oral semaglutide (50 mg) for persons with overweight or obesity.

METHODS: In a 71-week, double-blind, randomized, placebo-controlled trial conducted at 22 sites in four countries, we enrolled persons without diabetes who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or higher or a BMI of 27 or higher with at least one obesity-related complication. The participants were randomly assigned in a 2:1 ratio to receive oral semaglutide (25 mg) or placebo once daily, plus lifestyle interventions. The coprimary end points at week 64 were the percent change in body weight and a reduction of 5% or more in body weight; confirmatory secondary end points included reductions in body weight of 10% or more, 15% or more, and 20% or more and the change in the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function score.

RESULTS: A total of 205 participants were randomly assigned to receive oral semaglutide, and 102 to receive placebo. The estimated mean change in body weight from baseline to week 64 was -13.6% in the oral semaglutide group and -2.2% in the placebo group (estimated difference, -11.4 percentage points; 95% confidence interval, -13.9 to -9.0; P<0.001). Participants in the oral semaglutide group were significantly more likely than those in the placebo group to have body-weight reductions of 5% or more, 10% or more, 15% or more, and 20% or more (P<0.001 for all comparisons) and to have an improved IWQOL-Lite-CT Physical Function score (P<0.001). Gastrointestinal adverse events were more common with oral semaglutide than with placebo (74.0% vs. 42.2%).

CONCLUSIONS: Oral semaglutide at a dose of 25 mg once daily resulted in a greater mean reduction in body weight than placebo in participants with overweight or obesity. (Funded by Novo Nordisk; OASIS 4 ClinicalTrials.gov number, NCT05564117.).