OASIS 4 published: oral semaglutide 25 mg produces 13.6% weight loss

Results from OASIS 4, a randomized trial of a 25 mg once-daily semaglutide tablet in adults with overweight or obesity and without diabetes, have been published. Participants taking the pill lost an estimated 13.6% of their body weight at week 64, compared with 2.2% for those on placebo ^[1].

The trial ran 71 weeks, was double-blind and placebo-controlled, and was conducted at 22 sites in four countries ^[1]. It enrolled people without diabetes who had a body-mass index of 30 or higher, or 27 or higher with at least one weight-related health problem ^[1]. A total of 307 participants were randomly assigned in a 2-to-1 ratio: 205 to oral semaglutide 25 mg once daily and 102 to placebo, with both groups also receiving lifestyle support ^[1]. The study was funded by Novo Nordisk and is registered as NCT05564117 ^[1].

What the numbers showed

The two co-primary endpoints, both measured at week 64, were the percent change in body weight and the share of people losing 5% or more ^[1]. The estimated difference in weight change between groups was 11.4 percentage points in favor of the tablet (95% confidence interval, −13.9 to −9.0; P<0.001) ^[1].

People on oral semaglutide were also significantly more likely than those on placebo to hit thresholds of 5% or more, 10% or more, 15% or more, and 20% or more weight loss (P<0.001 for each), and to improve on the IWQOL-Lite-CT Physical Function score, a questionnaire measuring how weight affects day-to-day physical activity ^[1].

Side effects followed the familiar GLP-1 pattern. Gastrointestinal adverse events occurred in 74.0% of the oral semaglutide group versus 42.2% of the placebo group ^[1]. The published abstract does not break out which specific symptoms were most common, how many people stopped treatment because of side effects, or how many reached the full 25 mg dose, so those details are not available from this source.

One technical point worth flagging: trials like this often report weight loss two ways — an estimate that counts everyone as randomized, including people who stopped the drug early, and a second estimate of what happens if people stay on treatment as planned. The figure reported in the published abstract is a single estimated mean change of −13.6% ^[1]; the abstract does not spell out an alternative on-treatment analysis, so any higher number circulating for this trial cannot be verified from this source.

The paper describes oral semaglutide 25 mg as a possible alternative to injectable semaglutide 2.4 mg and to the higher-dose 50 mg tablet studied in earlier OASIS work ^[1]. The trial was classified as a phase 2 study ^[1]. Importantly, OASIS 4 compared the tablet against placebo, not head-to-head against the injection, so it does not establish whether the pill works as well as the shot.

Why it matters for patients

Semaglutide is the molecule in Ozempic and Wegovy, which are injected, and in Rybelsus, a tablet. A daily tablet studied specifically for weight management matters because needles, refrigeration, and injection-related anxiety keep some people from starting or staying on these drugs. Pills also move through a different manufacturing and supply chain than injectable pens, which can affect availability.

At the same time, the trade-offs in this trial look like those of other GLP-1 medicines. Roughly three in four participants on the tablet reported a gastrointestinal side effect, compared with a little over four in ten on placebo ^[1]. And 307 participants over 71 weeks is a modest, relatively short study by obesity-drug standards, which limits what it can say about rare risks or long-term results.

Cost, insurance coverage, and US regulatory status for a 25 mg weight-management tablet are not addressed in this source, so they remain unknown here.

What happens next

The results drew published correspondence in the New England Journal of Medicine on December 11, 2025, including letters from two groups of clinicians and a reply from the OASIS 4 study authors — Wharton, Duque do Vale, and Garvey, writing for the study group ^[1]. That exchange suggests continued debate among specialists about how the tablet fits alongside injectable options and bariatric surgery. Any timeline for regulatory review or US availability is not described in the source.