Oral semaglutide 25 mg produced 13.6% weight loss in adults without diabetes, trial reports

A once-daily 25 mg tablet of oral semaglutide produced an estimated mean weight loss of 13.6% at week 64 in adults with overweight or obesity who did not have diabetes, according to results of the OASIS 4 trial published in the New England Journal of Medicine ^[1]. Placebo participants lost an estimated 2.2% over the same period ^[1].

Semaglutide is the molecule in the injectable products Ozempic and Wegovy and in the oral product Rybelsus ^[1]. The report describes the 25 mg oral dose as a possible alternative to injectable semaglutide 2.4 mg and to a higher 50 mg oral dose ^[1].

What the trial measured

OASIS 4 was a 71-week, double-blind, randomized, placebo-controlled trial run at 22 sites in four countries ^[1]. It enrolled people without diabetes who had a body-mass index of 30 or higher, or a BMI of 27 or higher along with at least one obesity-related complication ^[1].

Participants were assigned in a 2-to-1 ratio to oral semaglutide 25 mg or placebo, taken once daily, alongside lifestyle interventions ^[1]. That worked out to 205 people on the drug and 102 on placebo — 307 in total ^[1].

The two main goals, measured at week 64, were the percentage change in body weight and the share of people losing at least 5% of their body weight ^[1].

The numbers

The estimated mean change in body weight from the start of the trial to week 64 was minus 13.6% in the oral semaglutide group and minus 2.2% in the placebo group, an estimated difference of 11.4 percentage points (95% confidence interval, minus 13.9 to minus 9.0; P<0.001) ^[1].

People taking the drug were significantly more likely than those taking placebo to lose at least 5%, 10%, 15% and 20% of their body weight, with P<0.001 for every one of those comparisons ^[1]. They were also significantly more likely to improve their score on a quality-of-life measure focused on physical function, the IWQOL-Lite-CT (P<0.001) ^[1].

The published abstract does not give the size of those categorical weight-loss results or the average starting weight of participants ^[1].

Side effects

Gastrointestinal adverse events were more common with oral semaglutide than with placebo, reported by 74.0% of participants on the drug compared with 42.2% on placebo ^[1]. The abstract does not break out which specific symptoms occurred or how many people stopped treatment because of them ^[1].

The trial was funded by Novo Nordisk and registered as NCT05564117 ^[1]. It is listed as a phase 2 clinical trial ^[1].

Why it matters for patients

All three semaglutide products sold in the United States are given by injection except Rybelsus, which is a tablet ^[1]. A once-daily pill at a higher dose than currently marketed oral forms could matter to people who dislike injections or have trouble with needles ^[1].

The 25 mg dose tested here is not the same as what is available now, and Novo Nordisk has not disclosed in the published report whether it plans to seek approval for a 25 mg oral semaglutide product for weight management ^[1]. The report also does not say what such a product would cost or when it might reach pharmacies ^[1].

The trial enrolled only people without diabetes, so the results do not directly describe how the 25 mg dose performs in people with type 2 diabetes ^[1]. Participants also received lifestyle interventions alongside the drug, so the weight-loss figures reflect the combination rather than the pill alone ^[1].

What happens next

The New England Journal of Medicine published three letters and an author reply about the trial on December 11, 2025 ^[1]. Those items are listed without abstracts ^[1]. Beyond the trial registration number, no timeline for regulatory review, additional analyses or further studies has been reported ^[1].