Oral Presentation Australian and New Zealand Obesity Society Annual Scientific Conference 2026

Efficacy and safety of oral semaglutide 25 mg in adults with overweight/obesity: the OASIS 4 RCT (144113)

Samantha Hocking 1 , W. Timothy Garvey 2 , Ruben Duque do Vale 3 , Tobias Karlsson 3 , Ildiko Lingvay 4 , Chaithra Shaji 5 , Domenica Rubino 6
  1. University of Sydney, Sydney, Australia
  2. Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
  3. Novo Nordisk A/S, Søborg, Denmark
  4. Department of Internal Medicine/Endocrinology and Peter O’ Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA
  5. Novo Nordisk, Bangalore, India
  6. Washington Center for Weight Management and Research, Arlington, VA, USA

Introduction: OASIS 4 (NCT05564117) evaluated once-daily oral semaglutide 25 mg (half the OASIS 1 [NCT05035095] dose) vs placebo in adults with overweight/obesity.

Methods: Participants (≥18 years; BMI ≥30 kg/m2 or ≥27 kg/m2 with ≥1 weight-related comorbidity) were randomised 2:1 to oral semaglutide escalated to 25 mg or placebo for 64 weeks, with lifestyle intervention. Co-primary endpoints were percent weight change and achievement of ≥5% weight loss (WL). Confirmatory secondary endpoints were ≥10% WL, ≥15% WL, ≥20% WL, and change in IWQOL-Lite-CT Physical Function score. Efficacy was analysed using the treatment policy estimand with in-trial data unless stated otherwise.

Results: Participants (semaglutide n=205; placebo n=102) were mostly female (78.8%), with a mean age of 48 years, and mean bodyweight of 105.9 kg. Mean weight change was
–13.6% with semaglutide vs –2.2% with placebo (p<0.0001), and –16.6% vs –2.7% (p<0.0001) using on-treatment data. More participants achieved ≥5% WL (79.2% vs 31.1%), ≥10% WL (63.0% vs 14.4%), ≥15% WL (50.0% vs 5.6%), and ≥20% WL (29.7% vs 3.3%) with semaglutide vs placebo (all p<0.0001). Greater improvements in IWQOL-Lite-CT Physical Function score occurred with semaglutide vs placebo (estimated treatment difference 7.7 points, 95% confidence intervals 3.3 to 12.2; p=0.0006). Significant improvements in cardiometabolic risk factors (glycated haemoglobin, fasting plasma glucose, C-reactive protein, triglycerides) were observed with semaglutide vs placebo. Incidence of all adverse events (AEs) was 93.1% for semaglutide and 85.3% for placebo. AEs leading to permanent treatment discontinuation (semaglutide 6.9% vs placebo 5.9%; mostly gastrointestinal AEs) were comparable between groups. Serious AEs were lower for semaglutide (3.9%) vs placebo (8.8%).

Conclusion: Once-daily oral semaglutide 25 mg significantly reduced bodyweight, increased physical function, and improved metabolic health in adults with overweight/obesity, with comparable efficacy to semaglutide 50 mg in the OASIS 1 trial. Safety and tolerability were consistent with the well-established profile of semaglutide.