OASIS 4 published in NEJM: oral semaglutide 25 mg matches injectable weight loss

The New England Journal of Medicine published results from OASIS 4 on September 17, 2025, showing that a once-daily 25 mg semaglutide tablet produced substantial weight loss in adults with obesity or overweight who did not have diabetes ^[1]. The trial was funded by Novo Nordisk, which makes semaglutide ^[1].

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 27 or higher with at least one obesity-related complication ^[1]. A total of 307 participants were randomly assigned 2 to 1 — 205 to oral semaglutide 25 mg and 102 to placebo — and everyone also received lifestyle support ^[1]. Treatment included a 12-week dose-escalation phase, then continued to week 64, followed by a 7-week period off treatment ^[4].

What the numbers showed

The main analysis, which counts everyone regardless of whether they kept taking the pill, found an estimated mean weight change at week 64 of −13.6% with oral semaglutide versus −2.2% with placebo — a difference of 11.4 percentage points (95% confidence interval, −13.9 to −9.0; P<0.001) ^[1]. In the analysis limited to participants who stayed adherent to treatment, mean weight loss was 16.6% versus 2.7% with placebo ^[4].

More people on the drug hit larger thresholds. Reductions of 5% or more, 10% or more, 15% or more and 20% or more were all significantly more common with oral semaglutide than placebo ^[1]. Among adherent participants, 34.4% lost at least 20% of their body weight, compared with 2.9% on placebo; in the broader analysis, close to 30% reached that mark versus 3.3% ^[4]. Scores on a quality-of-life measure of physical function also improved more with the drug ^[1].

Side effects followed the familiar GLP-1 pattern. Gastrointestinal adverse events occurred in 74.0% of the oral semaglutide group and 42.2% of the placebo group ^[1]. Serious adverse events were reported less often with oral semaglutide than placebo, at 3.9% versus 8.8% ^[4].

Later post hoc analyses from the same trial reported that 71.1% of participants who had prediabetes at the start had normal blood glucose at week 64 on semaglutide, versus 33.3% on placebo, and that people losing 15% or more had larger blood pressure drops ^[4].

Why it matters for patients

The practical question this trial addresses is whether a daily pill can deliver weight loss in the same range as weekly injections. OASIS 4 did not test that directly — there was no injectable comparison group, only placebo ^[1]. The study authors framed the 25 mg tablet as a possible alternative to injectable semaglutide 2.4 mg and to the higher-dose 50 mg oral formulation, but any comparison to injection numbers comes from separate trials, not head-to-head data ^[1].

The gap between the two weight-loss figures matters too. The 16.6% number reflects people who stayed on treatment as directed; the 13.6% number includes everyone assigned to the drug, including those who stopped or cut back ^[1][4]. Real-world results usually land closer to the second figure.

Stomach-related side effects were common, affecting nearly three-quarters of people on the pill ^[1]. The tablet is taken once daily on an empty stomach, a different routine from a weekly shot ^[3]. OASIS 4 also excluded people with diabetes, so it does not speak to that group ^[1][4].

What happens next

Novo Nordisk submitted the oral formulation to the European Medicines Agency and other regulators in the second half of 2025 ^[4]. The FDA approved the Wegovy pill on December 22, 2025, the first oral GLP-1 cleared for weight loss in adults and also indicated to reduce the risk of major cardiovascular events in adults with established cardiovascular disease and obesity or overweight ^[3][4]. Tablets come in 1.5 mg, 4 mg, 9 mg and 25 mg strengths and carry a boxed warning for thyroid C-cell tumors ^[3]. The company said it planned a full US launch in early January 2026 ^[4]. Long-term data beyond 71 weeks for this dose are not yet available in these sources.