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

Oral Semaglutide 25 mg Versus Orforglipron 36 mg in Obesity: A Population-Adjusted Indirect Treatment Comparison (#106)

Tomasz Block 1 2 , Wojciech Michalak 3 , Christian Laugesen 4 , Naveen Rathor 4 , Phoebe Cowley 5 , Rohan Chowdhury 5 , Martin Bøg 4
  1. Department of Endocrinology and Diabetes, Alfred Health, Melbourne, VIC, Australia
  2. Department of Diabetes, School of Translational Medicine, Monash University, Melbourne, VIC, Australia
  3. Novo Nordisk Inc., Plainsboro, NJ, USA
  4. Novo Nordisk A/S, Søborg, Denmark
  5. Petauri Evidence, Bicester, United Kingdom

Introduction

Oral semaglutide peptide, and orforglipron, a non-peptide small-molecule, are glucagon-like peptide-1 receptor agonists (GLP-1RAs) that reduced body weight (BW) in individuals with overweight or obesity in the OASIS-4 and ATTAIN-1 phase 3 trials. In the absence of head-to-head data, this indirect treatment comparison (ITC) assessed weight-loss efficacy and tolerability between oral semaglutide 25 mg and oral orforglipron 36 mg.

Methods

OASIS-4 and ATTAIN-1 were comparable in key inclusion criteria (BMI ≥30 kg/m2 or BMI ≥27 kg/m2 with ≥1 obesity-related complication), estimands, trial design, and 52-week maintenance dosing. Due to between-trial differences in sex and glycaemic status, a simulated treatment comparison was used to assess percentage change from baseline in BW. A two-stage matching-adjusted indirect comparison was used for tolerability outcomes: discontinuations due to adverse events (AEs) and gastrointestinal (GI) AEs. Analyses were adjusted for baseline BW, glycaemic status and sex. Treatment effects in ATTAIN-1 population were compared. 

Results

Across treatment policy and hypothetical estimands, oral semaglutide 25 mg demonstrated significantly greater reductions in BW from baseline versus orforglipron 36 mg: mean differences [95% CI] of ‑3.16%-points [-5.94, -0.38] and -3.04%-points [-5.76, -0.31], respectively. Orforglipron 36 mg was associated with significantly higher odds of discontinuations due to any AEs (odds ratio [OR] [95% CI]: 4.11 [1.30, 13.03]) and GI AEs (OR [95% CI]: 13.86 [2.00, 96.01]) versus semaglutide 25 mg. 

Conclusion

In this ITC, oral semaglutide 25 mg demonstrated significantly greater weight loss versus orforglipron 36 mg in individuals with overweight or obesity. Orforglipron 36 mg was associated with significantly higher risk of discontinuations due to any AEs, including GI AEs, although this should be interpreted with care due to small event numbers. The results provide valuable insight into the relative efficacy and tolerability of these treatments. Further research is warranted to evaluate comparative effects on cardiometabolic risk factors.