- OASIS 4 was a randomized, double‑blind, placebo‑controlled phase 3 trial (2:1 randomisation) of oral semaglutide 25 mg once daily for 64 weeks in adults with BMI ≥30 or ≥27 plus a weight‑related comorbidity.
- 28.8% were early responders (≥10% weight loss by week 16), averaging 13.2% at week 16 and 21.6% by week 64, while non‑responders still lost 11.5%; overall mean weight loss was 17% vs 2.7% with placebo.
- Among participants with poor physical function, 77.3% on oral semaglutide achieved clinically meaningful function improvements versus 42.9% on placebo.
- Indirect comparisons showed greater mean weight loss with oral semaglutide versus orforglipron 36 mg, orforglipron had ~14× higher odds of discontinuation for gastrointestinal side effects, and 84% of respondents in a patient‑preference study favoured a profile like oral semaglutide.
Key efficacy results
In OASIS 4 (oral semaglutide 25 mg once daily), 28.8% were early responders (≥10% weight loss by week 16), averaging 13.2% loss at week 16 and 21.6% by week 64; non‑responders still lost 11.5% by week 64 and the overall mean was 17% versus 2.7% with placebo.
Mobility and physical function
Among participants with poor physical function, 77.3% on oral semaglutide achieved clinically meaningful improvements in function scores (assessing range of motion and stamina) versus 42.9% on placebo, with weight loss in this subgroup similar to the overall treatment group.
Comparative analyses
Indirect ORION comparisons reported greater mean weight loss with oral semaglutide versus orforglipron 36 mg and found orforglipron associated with approximately 14× higher odds of discontinuation for gastrointestinal adverse events; the OPTIC patient‑preference study indicated 84% of respondents favored a treatment profile similar to oral semaglutide over orforglipron.
Safety and trial design
OASIS 4 was a randomized, double‑blind, placebo‑controlled phase 3 trial (2:1 randomization) in adults with BMI ≥30 or ≥27 plus a weight‑related comorbidity without type 2 diabetes, run for 64 weeks; the most common adverse events were gastrointestinal, mostly mild to moderate and diminishing over time, consistent with the GLP‑1 receptor agonist class.
