Relationship of early rapid weight loss to efficacy and safety of tirzepatide and semaglutide for obesity: SURMOUNT-5 post hoc analysis.

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. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT05822830.