University of Oklahoma Health Sciences Center

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Author/s:

Sean Wharton, Ildiko Lingvay, Pawel Bogdanski, Ruben Duque do Vale, Stephan Jacob, Tobias Karlsson, Chaithra Shaji, Domenica Rubino, W. Timothy Garvey

Date Added:

October 7, 2025

Journal/Publication:

New England Journal of Medicine

Publication Date:

September 18, 2025

Issue:

Volume:

393

URL:

Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa2500969

PMID (1):

40934115

Keywords

Semaglutide

overweight

MeSH

RPR Commentary

Oral semaglutide 25mg daily resulted in a 14% reduction in weight in 1.4 years. James W. Mold, MD, MPH

Abstract

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.)

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