BACKGROUND AND PURPOSE:

• The OASIS 1 Trial found that 50 mg oral semaglutide reduced body weight and cardiovascular risk in individuals with overweight and obesity
  • A dose of 25 mg may also be appropriate for this population
• Wharton et al. (NEJM, 2025) evaluated the efficacy and safety of a lower 25 mg oral semaglutide dose for participants with overweight or obesity

METHODS:

• 71-week, double-blind, randomized, placebo-controlled trial
  • OASIS 4 Trial
  • 22 sites in four countries (Canada, Germany, Poland, and the US)
• Participants
  • Without diabetes
  • BMI ≥30 or BMI ≥27 with at least one obesity-related complication
• Interventions
  • Oral semaglutide, 25 mg, once daily
  • Placebo
• Study design
  • All participants were counseled in lifestyle interventions
• Primary outcomes
  • Percent change in body weight at week 64
  • Reduction of 5% or more in body weight
• Secondary outcomes
  • Reductions in body weight of ≥10% | ≥15% | ≥20%
  • Change in the Impact of Weight on Quality of Life–Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function score

RESULTS:

• Oral semaglutide: 205 | Placebo: 102
• There was a significantly greater mean change in body weight at week 64 in the oral semaglutide group
  • Oral semaglutide: –13.6% | Placebo: –2.2%
  • Estimated difference, −11.4 percentage points (95% CI, −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%, ≥10%, ≥15% and ≥20% (P<0.001 for all comparisons)
• Those who received oral semaglutide also had improved IWQOL-Lite-CT Physical Function score (P<0.001)
• Gastrointestinal adverse events were more common with oral semaglutide
  • Oral semaglutide: 74.0% | Placebo: 42.2%

CONCLUSION:

• For individuals with overweight or obesity and without diabetes, once daily oral semaglutide (25 mg) led to significantly greater body weight reduction vs placebo
• The authors state

In our trial, oral semaglutide at a dose of 25 mg once daily led to a clinically relevant mean reduction in body weight of 13.6%

Almost a third of the participants in the oral semaglutide group had a reduction in body weight of 20% or more

Learn More – Primary Sources:

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