A Phase 3, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Retatrutide Compared to Tirzepatide in Adults Who Have Obesity

ClinicalTrials13 Apr 2026·Phase 3● 8/10i

A Phase 3, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Retatrutide Compared to Tirzepatide in Adults Who Have Obesity

Eli Lilly and Company

Eli Lilly is conducting a Phase 3 head-to-head trial comparing retatrutide versus tirzepatide in adults with obesity. The double-blind study targets 800 participants over 89 weeks with primary endpoint of percent body weight change, completing December 2026. This represents the first direct comparison between Eli Lilly's next-generation triple receptor agonist retatrutide and its approved dual agonist tirzepatide in obesity. The trial positions Eli Lilly to potentially establish superiority claims for retatrutide ahead of expected regulatory submissions.

Strategic signal

Eli Lilly is building head-to-head superiority data against its own Zepbound to support premium positioning for retatrutide. This internal competition mirrors Novo's CagriSema strategy against Wegovy, where newer combination therapies require demonstrated superiority over existing blockbusters. US payers will likely demand tirzepatide step-through requirements before covering retatrutide unless efficacy gaps are substantial. The 89-week duration suggests Eli Lilly is targeting durable weight loss claims beyond current obesity standards.

GLP-1Weight lossDrug comparisonsEli Lilly

Original Abstract

The main purpose of this study is to evaluate the efficacy and safety of retatrutide compared to tirzepatide in adults who have obesity. The study will last about 89 weeks. | Condition(s): Obesity | Primary endpoint(s): Percent Change from Baseline in Body Weight | Enrollment: 800 (estimated) | Phase: Phase 3 | Sponsor: Eli Lilly and Company | Expected completion: 2026-12 | Status: Active Not Recruiting | Last update: 2026-04-13

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