Relationship of Early Rapid Weight Loss to Efficacy and Safety of Tirzepatide and Semaglutide for Obesity: Surmount-5 Post Hoc Analysis

Authors

• Louis J Aronne
• Deborah B Horn
• Alexander D Kokkinos
• Beverly L Falcon
• Hui Wang
• Hunter T Hoffmann
• Clare J Lee
• Julia P Dunn

Language

English

Publication Date

7-1-2026

Journal

The American Journal of Medicine

DOI

10.1016/j.amjmed.2026.03.010

PMID

41865857

Abstract

Background: A knowledge gap remains in how the rate of body weight reduction impacts efficacy and safety of obesity management medications. This SURMOUNT-5 post hoc analysis aimed to define rapid responders and evaluated efficacy and safety of tirzepatide versus. semaglutide in rapid responders versus non-rapid responders.

Methods: Rapid responders and non-rapid responders were defined as participants that obtained ≥ 15% and < 15% body weight reduction by Week 24, respectively. Baseline characteristics, and proportion of participants achieving body weight reduction thresholds by Week 72 were assessed. End-of-study safety and gastrointestinal adverse events measures were summarized.

Results: Overall, 32.3% were rapid responders (tirzepatide: 44%, semaglutide: 21%). The proportions of participants achieving body weight reduction thresholds by Week 72 were higher for rapid responders versus non-rapid responders. Safety trends for tirzepatide and semaglutide were similar between responder groups. A numerically higher number of gastrointestinal/hepatobiliary adverse events were reported in rapid responders. Study treatment completion was similar among rapid responders and non-rapid responders for both treatments.

Conclusions: In this post hoc analysis of SURMOUNT-5, a greater proportion of tirzepatide-treated participants in both responder groups achieved all body weight reduction thresholds versus semaglutide. Although rapid responders experienced more gastrointestinal/hepatobiliary adverse events in both treatments, this did not affect rates of study treatment completion relative to non-rapid responders.

Keywords

Adult, Female, Humans, Male, Middle Aged, Anti-Obesity Agents, Glucagon-Like Peptides, Obesity, Semaglutide, Tirzepatide, Treatment Outcome, Weight Loss, Early weight reduction, Rapid weight reduction, Semaglutide, Tirzepatide

Comments

Trial registration: clinicaltrials.gov identifier NCT05822830.

Published Open-Access

yes

Recommended Citation

Aronne, Louis J; Horn, Deborah B; Kokkinos, Alexander D; et al., "Relationship of Early Rapid Weight Loss to Efficacy and Safety of Tirzepatide and Semaglutide for Obesity: Surmount-5 Post Hoc Analysis" (2026). Faculty, Staff and Student Publications. 4510.
https://digitalcommons.library.tmc.edu/uthmed_docs/4510