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ClinicalTrials20 Apr 2026·Phase 3

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Event-Driven Study to Investigate the Effect of Retatrutide on the Incidence of Major Adverse Cardiovascular Events and Major Adverse Kidney Events in Participants With Body Mass Index ≥27 kg/m2 and Atherosclerotic Cardiovascular Disease and/or Chronic Kidney Disease

Eli Lilly and Company

Phase 3 cardiovascular and kidney outcomes trial testing retatrutide in adults with BMI ≥27 kg/m² and atherosclerotic cardiovascular disease and/or chronic kidney disease. Enrollment targets 10,000 participants in a double-blind, placebo-controlled, event-driven design running approximately 5 years through February 2029. Eli Lilly advances retatrutide into major outcomes territory, competing directly with established GLP-1 agents that already hold cardiovascular indications like Wegovy and future tirzepatide expansions. This represents the largest cardiovascular outcomes program for any triple agonist to date.

Strategic signal

Eli Lilly positions retatrutide for cardiovascular outcomes before obesity approval, mirroring Novo's successful Wegovy MACE expansion strategy in March 2024. The 10,000-patient scale signals Lilly's confidence in competing against established GLP-1 cardiovascular claims from Wegovy and potential future tirzepatide MACE data. US CMS and EU HTA bodies will compare retatrutide's risk reduction profile against existing GLP-1 cardiovascular evidence when evaluating reimbursement tiers. The dual MACE/kidney endpoint combination targets high-value patient populations already covered by competitor agents.

CardiovascularKidneyWeight lossEli Lilly

Original Abstract

The main purpose of this study is to determine if retatrutide can significantly lower the incidence of serious heart-related complications or prevent the worsening of kidney function. The trial will enroll adults with body mass index 27 kg/m\^2 or higher and Atherosclerotic Cardiovascular Disease and/or chronic kidney disease. The study will last for about 5 years. Participants will have up to 27 clinic visits with the study doctor. | Condition(s): Atherosclerotic Cardiovascular Disease (ASCVD); Chronic Kidney Disease (CKD) | Primary endpoint(s): Time to First Occurrence of Composite Endpoints; Time to First Occurrence of Composite Endpoint of End Stage Kidney Disease (ESKD), ≥ 40% Sustained Decline in Estimated Glomerular Filtration Rate (eGFR), CV Death or Renal Death | Enrollment: 10,000 (estimated) | Phase: Phase 3 | Sponsor: Eli Lilly and Company | Expected completion: 2029-02 | Status: Active Not Recruiting | Last update: 2026-04-20

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GLP-1CardiovascularEli Lilly

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