NCT07165028

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

A Master Protocol for a Randomized, Controlled, Clinical Trial of Multiple Pharmacologic Agents in Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease Who Are at Increased Risk of Developing Major Adverse Liver Outcomes

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 4,500 (estimated)
• Sponsor: Eli Lilly and Company · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The main purpose of the SYNERGY-OUTCOMES study is to find out whether retatrutide and tirzepatide can prevent major adverse liver outcomes (MALO) in people with high-risk metabolic dysfunction-associated steatotic liver disease (MASLD). The study will enroll adults who have MASLD based on non-invasive tests (NITs), which indicate they are more likely to develop MALO. Participants will be randomly assigned within a Master Protocol to receive either retatrutide (N1T-MC-RT01), tirzepatide (N1T-MC-TZ01) or placebo. The trial plans to enroll about 4,500 adults and will run for approximately 224 weeks. Participants may have up to approximately 25 to 30 clinic visits throughout the study to monitor their health, complete study procedures, and assess liver function and disease progression. Once the study is complete, eligible participants may participate in an optional 2-year extension study, in which all participants will receive either retatrutide or tirzepatide, even if they received placebo in the main study.

Conditions

• Metabolic Dysfunction-Associated Steatotic Liver Disease

Interventions

Type	Name	Description
DRUG	Tirzepatide	Administered SC
DRUG	Retatrutide	Administered SC
DRUG	Placebo	Administered SC

Timeline

• Start date: 2025-10-15
• Primary completion: 2030-08-01
• Completion: 2032-08-01
• First posted: 2025-09-10
• Last updated: 2026-04-17

Locations

561 sites across 35 countries: United States, Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czechia, France, Germany, Hong Kong, Hungary, India, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Puerto Rico, Romania, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom

Regulatory

• FDA-regulated drug study