Oral semaglutide 25 mg lowered weight 13.6% in OASIS 4 obesity trial
A 25 mg daily pill version of semaglutide produced double-digit weight loss in a late-stage trial, giving adults with obesity a non-injection option that was later approved by the FDA.
Once-daily oral semaglutide 25 mg produced a mean 13.6% reduction in body weight over 64 weeks in adults with overweight or obesity, compared with 2.2% for placebo, according to results from the OASIS 4 trial published September 17, 2025 in the New England Journal of Medicine [1]. The estimated difference between groups was 11.4 percentage points (95% confidence interval, −13.9 to −9.0; P<0.001) [1].
How the trial was run
OASIS 4 was a 71-week, double-blind, randomized, placebo-controlled trial conducted at 22 sites in four countries [1]. It enrolled 307 people without diabetes who had a body-mass index of 30 or higher, or a BMI of 27 or higher with at least one obesity-related complication [1]. Participants were assigned 2:1 to oral semaglutide 25 mg (205 people) or placebo (102), and everyone also received lifestyle interventions [1]. Treatment included a 12-week dose-escalation phase followed by continued dosing through week 64, then a 7-week off-treatment follow-up [4]. Novo Nordisk funded the study [1].
The 13.6% figure is the treatment-policy analysis, which counts everyone as randomized regardless of whether they stayed on the drug [1][4]. Among participants who adhered to treatment, mean weight loss was 16.6%, compared with 2.7% on placebo [4]. In that adherent group, 34.4% lost at least 20% of their body weight, versus 2.9% on placebo; in the treatment-policy analysis, nearly 30% reached that threshold versus 3.3% [4].
Participants on oral semaglutide were significantly more likely than those on placebo to lose 5%, 10%, 15% or 20% or more of their body weight (P<0.001 for all comparisons) and to report improved scores on the IWQOL-Lite-CT Physical Function measure (P<0.001) [1].
Gastrointestinal adverse events occurred in 74.0% of the oral semaglutide group versus 42.2% of the placebo group [1]. Serious adverse events were reported less often with oral semaglutide, 3.9%, than with placebo, 8.8% [4].
Post hoc analyses presented later found that 71.1% of participants who had prediabetes at baseline reached normal blood glucose, versus 33.3% on placebo [4]. Among participants who lost at least 15% of body weight, average systolic blood pressure fell 10.1 mmHg in the semaglutide group versus 4.1 mmHg with placebo, and diastolic pressure fell 4.3 mmHg versus 1.1 mmHg [4]. A pooled analysis of OASIS 4 and the STEP trials found mean weight loss of 18.2% in pre-menopausal participants, 15.0% in peri-menopausal participants and 15.7% in post-menopausal participants [4].
The trial compared the pill with placebo. A head-to-head comparison of oral semaglutide 25 mg against injectable semaglutide 2.4 mg was not part of this study and results of such a comparison have not been reported [1].
Lead study author Sean Wharton said: "People with overweight or obesity have individual preferences, and with oral semaglutide as a potential new treatment option, more of those who are not on treatment today may consider starting GLP-1 treatment" [4].
Why it matters for patients
The FDA approved the Wegovy pill (semaglutide) on December 22, 2025, making it the first oral GLP-1 approved for weight loss in adults; it is also indicated to reduce the risk of major adverse cardiovascular events, including death, heart attack or stroke [4]. Wegovy tablets are approved in four strengths — 1.5 mg, 4 mg, 9 mg and 25 mg — and are taken once daily on an empty stomach [3].
The Wegovy label carries a boxed warning for increased risk of thyroid C-cell tumors, and lists warnings for acute pancreatitis, gallbladder disease, low blood sugar, acute kidney injury, hypersensitivity reactions, increased heart rate and suicidal behavior and ideation, among others [3]. Common adverse reactions reported at rates of 5% or more include nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue and indigestion [3].
The trial excluded people with diabetes, so these results do not describe how the pill performs in that group [1]. OASIS 4 was designed to test weight outcomes over about 14 months; whether weight loss is maintained after stopping treatment was not reported [1][4].
Novo Nordisk said at the time of approval that the pill would carry "the most affordable self-pay price to date in a GLP-1 for obesity," but no specific price was disclosed in that statement [4].
What happens next
Novo Nordisk said it was prepared for a full US launch of the Wegovy pill in early January 2026, with manufacturing at its North Carolina facilities [4]. The company also said it submitted the oral formulation to the European Medicines Agency and other regulators in the second half of 2025; decisions from those agencies have not been reported [4].
Sources
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