A Master Protocol for a Randomized, Controlled Trial of Retatrutide and Tirzepatide in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease at High Risk of Major Adverse Liver Outcomes

What this Trial Is About

Researchers are evaluating whether two drugs, retatrutide and tirzepatide, can prevent serious liver problems in adults with metabolic dysfunction-associated steatotic liver disease MASLD who are at high risk based on non-invasive tests. This Phase 3 randomized clinical trial plans to enroll about 4,500 adults and will last approximately 224 weeks, including up to 25 to 30 clinic visits to monitor health and liver disease progression. The study is sponsored by Eli Lilly and Company. Participants will be randomly assigned to receive either retatrutide, tirzepatide, or a placebo, all given by subcutaneous injection. After completing the main study, eligible participants may join a 2-year extension where everyone receives either retatrutide or tirzepatide, regardless of their original group. This Master Protocol evaluates multiple pharmacologic agents under controlled conditions. Throughout the study, participants will undergo various assessments including liver function tests, imaging to measure liver stiffness and fat content, and body weight measurements. Researchers will track the time to major adverse liver outcomes and cardiovascular events. Safety and disease progression will be closely monitored, and the study includes evaluations at baseline, week 104, and up to study completion.

A Master Protocol of Multiple Agents in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (SYNERGY-Outcomes)