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Testing retatrutide and tirzepatide to prevent serious liver complications in adults with high‑risk MASLD

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

Phase 3 Interventional Eli Lilly and Company · NCT07165028

This trial tests whether retatrutide or tirzepatide can prevent major liver complications in adults with high‑risk metabolic dysfunction‑associated steatotic liver disease identified by noninvasive tests.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment4500 (estimated)
Ages18 Years and up
SexAll
SponsorEli Lilly and Company Industry-sponsored
Locations561 sites (Tuscaloosa, Alabama and 560 other locations)
Trial IDNCT07165028 on ClinicalTrials.gov

What this trial studies

SYNERGY‑Outcomes is a randomized, phase 3 master protocol that assigns adults with high‑risk MASLD by noninvasive tests to retatrutide, tirzepatide, or placebo. The study plans to enroll about 4,500 participants and follow them for roughly 224 weeks with around 25–30 clinic visits to monitor liver function and clinical events. Key entry criteria use liver fat, ELF score, and VCTE liver stiffness to select people at higher risk of major adverse liver outcomes. After the main study, eligible participants may join an optional two‑year extension during which all participants can receive retatrutide or tirzepatide.

Who should consider this trial

Good fit: Adults with MASLD identified by noninvasive tests—liver fat ≥8%, ELF 9.0–10.8, and VCTE liver stiffness 10–<20 kPa—who have BMI ≥25, no other liver disease, no prior liver decompensation, HbA1c ≤10%, and stable recent weight are the intended candidates.

Not a fit: People with milder disease below the NIT thresholds, other causes of liver disease, prior decompensated liver disease, type 1 diabetes, BMI <25, recent significant weight loss, or very high uncontrolled diabetes are unlikely to be eligible or to benefit from this study.

Why it matters

Potential benefit: If successful, these medications could lower the risk of major adverse liver outcomes such as progression to decompensated liver disease, liver‑related transplant, or liver‑related death in people with high‑risk MASLD.

How similar studies have performed: Previous trials of tirzepatide and other incretin‑based therapies have shown substantial weight loss and reductions in liver fat and fibrosis biomarkers, and early data for retatrutide show strong metabolic and liver‑fat improvements, but using these drugs specifically to prevent major liver outcomes is a novel and unproven approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Have liver fat content ≥8%
* Have ELF score of ≥9 and ≤10.8 at screening
* Have VCTE LSM ≥10 kilopascal (kPa) and \<20 kPa at screening

Exclusion Criteria:

* Have any other type of liver disease other than MASLD
* Have a body mass index (BMI) \<25 kilogram per square meter (kg/m2)
* Prior decompensated liver disease (history of esophageal/gastric varices, ascites, hepatic encephalopathy)
* Have lost more than 11 pounds within the 3 months prior to screening
* Have a hemoglobin A1c (HbA1c) greater than 10%
* Have type 1 diabetes

Where this trial is running

Tuscaloosa, Alabama and 560 other locations

+511 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metabolic Dysfunction-Associated Steatotic Liver DiseaseNonalcoholic SteatohepatitisNASHFatty LiverFatty Liver DiseaseSLDMetabolic Dysfunction-Associated Fatty Liver DiseaseMAFLD
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.