If you wish to report an adverse event or product complaint, please call 1-800-LILLYRX (1-800-545-5979)
Retatrutide-Diabetes
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling.
Is retatrutide being studied in patients with metabolic dysfunction-associated steatotic liver disease?
Retatrutide is being studied in a phase 3 study to prevent major adverse liver outcomes in adults with high-risk metabolic dysfunction-associated steatotic liver disease (MASLD). The study spans approximately 224 weeks, with an optional 2-year extension.
What is the SYNERGY-Outcomes Clinical Study?
Retatrutide is not approved nor indicated to treat people for MASLD.
SYNERGY-Outcomes is an ongoing phase 3 study designed to simultaneously assess retatrutide and tirzepatide treatment for the prevention of major adverse liver outcomes (MALO) in adults with high-risk MASLD. Using a master protocol, participants will be randomly assigned to receive either
- retatrutide,
- tirzepatide, or
- placebo.1
The study will enroll approximately 4,500 adults who have MASLD based on non-invasive tests (NITs), which indicate the participant is more likely to develop MALO. The trial is expected to run for approximately 224 weeks, after which an optional 2-year extension study will be available for eligible participants, who will either remain on active treatment or switch from placebo to retatrutide or retatrutide. Please see SYNERGY-Outcomes Study Design for visual representation.1
Inclusion and Exclusion Criteria
Inclusion Criteria |
Exclusion Criteria |
Liver biopsy is not needed for study enrollment. |
|
Abbreviations: BMI = body mass index; ELF = enhanced liver fibrosis; HbA1c = hemoglobin A1c; kPa = kilopascal; MASLD = metabolic dysfunction-associated steatotic liver disease; VCTE LSM = vibration-controlled transient elastography liver stiffness measurement.
Outcome Measures
The primary outcome is the time to first occurrence of any component of the composite endpoint for MALO compared to placebo from baseline up to study completion.1
The composite endpoint includes
- progression to cirrhosis
- development of large esophageal varices, gastric varices, or development of varices needing treatment
- development of ascites
- development of hepatic encephalopathy
- evidence of active or recent variceal hemorrhage
- increase in model for end-stage liver disease (MELD) from ≤12 to ≥15
- liver transplantation, or
- all-cause mortality.1
Secondary outcomes include change from baseline in
- Enhanced Liver Fibrosis (ELF) Score (to Week 104)
- Vibration-Controlled Transient Elastography Liver Stiffness Measurement (VCTE LSM) (to Week 104)
- percent change in liver fat content (to Week 104)
- aspartate aminotransferase (AST) (to study completion)
- alanine aminotransferase (ALT) (to study completion)
- body weight (to study completion), and
- Non-alcoholic steatohepatitis-CHECK Score (NASH-CHECK) (to Week 104).1
In addition, from baseline to study completion, time to
- occurrence of progression to cirrhosis, and
- first occurrence of any component event of the composite endpoint of major adverse cardiovascular events (MACE-3, which includes nonfatal myocardial infarction, nonfatal stroke, cardiovascular death).1
Figure Description: SYNERGY-Outcomes is an ongoing phase 3 study designed to simultaneously assess retatrutide and tirzepatide treatment for the prevention of MALO in adults with high-risk MASLD.
Abbreviations: BMI = body mass index; ELF = enhanced liver fibrosis; HbA1c = hemoglobin A1c; ISA = intervention-specific appendices; kPa = kilopascal; LFC = liver fat content; MALO = major adverse liver outcome; MASLD = metabolic dysfunction-associated steatotic liver disease; MELD = model for end-stage liver disease; NIT = non-invasive test; VCTE LSM = vibration-controlled transient elastography liver stiffness measurement.
References
1A master protocol for the randomized, controlled, clinical trial of multiple pharmacologic agents in adults participants with metabolic dysfunction-associated steatotic liver disease who are at increased risk of developing major adverse liver outcomes. ClinicalTrials.gov identifier: NCT07165028. Updated September 10, 2025. Accessed September 11, 2025. https://clinicaltrials.gov/study/NCT07165028
Date of Last Review: August 25, 2025