What does this research mean for the field?

Patients with overweight or class I obesity treated with oral semaglutide experience similar or greater improvements in cardiometabolic outcomes and weight loss compared to patients with class II or III obesity. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This analysis aims to evaluate the impact of oral semaglutide on cardiometabolic outcomes across different BMI classes.

June 7, 2026

2838-LB: Cardiometabolic Effects of Semaglutide in OASIS 4 Participants by BMI Class

Key Points

This analysis aims to evaluate the impact of oral semaglutide on cardiometabolic outcomes across different BMI classes.
Post hoc analysis of OASIS 4 trial participants grouped by baseline BMI.
Participants received oral semaglutide 25mg for 64 weeks.
Comparisons were made on changes in body weight and biomarkers between cohorts.
Participants with overweight/obesity class I experienced similar body weight changes to those in classes II/III.
23% of the overweight/obesity class I cohort shifted to low risk by week 64.
Clinical biomarkers improved numerically more in the overweight/obesity class I group compared to obesity class II/III.

Abstract

Introduction and Objective: The benefits of oral semaglutide (sema) in people with overweight/obesity class I are understudied. This post hoc analysis of the OASIS 4 trial assessed the effect of oral sema on cardiometabolic outcomes by baseline BMI class. Methods: Participants (pts) in OASIS 4 randomized to receive oral sema 25mg for 64 weeks were grouped by baseline BMI. Changes from baseline in body weight and biomarkers were compared in overweight/obesity class I (BMI 27-35) vs obesity class II/III (BMI ≥35) cohorts. Results: Pts with overweight/obesity class I (n=85) achieved similar changes in body weight vs those in obesity classes II/III (n=119; Table). A comparable proportion of pts shifted to lower BMI classes by week 64. At baseline, no pts were in the National Institute for Health and Care Excellence low health risk category based on waist to height ratio and 100% of the obesity class II/III cohort was considered high risk. By week 64, 23% of the overweight/obesity class I cohort shifted to low risk and 30% of the obesity class II/III cohort to low or increased risk. Changes from baseline in most clinical biomarkers were numerically greater in the overweight/obesity class I vs the obesity class II/III cohort. Conclusion: Pts with overweight/obesity class I treated with oral sema had similar or greater improvements in cardiometabolic outcomes vs the obesity class II/III cohort. Sema initiation at lower baseline BMI may prevent the development or worsening of obesity-related complications. Disclosure D. Rubino: Other - Advisory panel, research support, shareholder; Current; AbbVie Inc. Other - steering committee, research support; Current; Amgen Inc. Other - advisory panel, steering committee, research support; Current; AstraZeneca. Other - advisory panel, research support; Current; Boehringer Ingelheim International GmbH. Other - advisory panel, speaker, research support,; Current; Novo Nordisk. Consultant; Current; Lilly, Shionogi Current; Neurocrine Biosciences, Inc., Regeneron Pharmaceuticals Inc. Consultant; Current; Pfizer Inc., Roche Pharmaceuticals, Cytoki. Other - advisory, research support; Current; Terns Pharmaceutical. Advisory Panel; Current; Neuraly Inc. Consultant; Current; Ferring Pharmaceuticals. Consultant; Ended; NodThera. L. Wilson: Employee; Current; Novo Nordisk. A. Traina: Employee; Current; Novo Nordisk. Stock/Shareholder; Current; Novo Nordisk. N. Rathor: None. J. Wang: None. M. Knight: Consultant; Current; Novo Nordisk, Boehringer Ingelheim International GmbH. Consultant; Ended; Currax Pharmaceuticals.

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