Oral glucagon-like peptide-1 receptor agonist options for obesity continue to expand, but dose-specific data remain limited across patient populations. A study published in Diabetes, Obesity and Metabolism used population pharmacokinetic and exposure-response modelling to estimate the efficacy and safety of once-daily oral Semaglutide 25 mg in individuals with overweight or obesity, with and without type 2 diabetes mellitus (T2DM).

Oral semaglutide 25 mg was approved for obesity treatment based on historical semaglutide data and findings from the OASIS program. Two virtual studies were conducted: a modelled Phase 2 trial to evaluate efficacy across oral semaglutide dose levels, and a modelled Phase 3 trial to assess efficacy in a population with overweight or obesity and T2DM.

Among participants treated with oral semaglutide 25 mg in OASIS 4, 82.2% achieved exposure levels within the same range observed with once-weekly subcutaneous semaglutide 2.4 mg in STEP 1.

In the simulated analyses, oral semaglutide 25 mg produced significantly greater weight reduction than placebo. Estimated weight loss in participants with overweight or obesity and T2DM was 9.4% using the trial product estimand and 7.8% using the treatment policy estimand. In participants with overweight or obesity without T2DM, corresponding reductions were 16.3% and 14.7%.

These findings suggest oral semaglutide 25 mg may provide exposure and weight-loss efficacy comparable to subcutaneous semaglutide 2.4 mg in people with overweight or obesity, regardless of T2DM status.