A Phase 3 interventional study of Tirzepatide and Retatrutide in Metabolic Dysfunction-Associated Steatotic Liver Disease, sponsored by Eli Lilly and Company. Recruiting at 563 sites in 34 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-08.
Sponsored by Eli Lilly and Company · Phase 3, Interventional, and Treatment
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.
1,617 studies on the registry are indexed under Non-alcoholic Fatty Liver Disease; 324 are open to participants now.
This study's planned enrollment of 4,500 is above the median of 60 across 1,176 interventional studies indexed under Non-alcoholic Fatty Liver Disease.
Browse Non-alcoholic Fatty Liver Disease studies →Eli Lilly and Company is the lead sponsor of 2,106 studies on the registry; 152 are open to participants now.
Of its 536 completed or terminated interventional studies of FDA-regulated products, 357 (67%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive tirzepatide subcutaneously (SC)
Drug: Tirzepatide
Participants will receive placebo SC
Drug: Placebo
Participants will receive retatrutide SC
Drug: Retatrutide
Participants will receive placebo SC
Drug: Placebo
Administered SC
Also known as: LY3298176
Administered SC
Also known as: LY3437943
Administered SC
Time to First Occurrence of Any Component of the Composite Endpoint for Major Adverse Liver Outcomes (MALO)
Composite endpoint comprised of 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, all-cause mortality
Time frame: Baseline up to Study Completion (about 224 weeks)
Change from Baseline in Enhanced Liver Fibrosis (ELF) Score
Time frame: Baseline, Week 104
Change from Baseline in Vibration-Controlled Transient Elastography Liver Stiffness Measurement (VCTE LSM)
Time frame: Baseline, Week 104
Percent Change from Baseline in Liver Fat Content (LFC)
Time frame: Baseline, Week 104
Time to Occurrence of Progression to Cirrhosis
Time frame: Baseline up to Study Completion (about 224 weeks)
Change from Baseline in Aspartate Aminotransferase (AST)
Time frame: Baseline, Study Completion (about 224 weeks)
Change from Baseline in Alanine Aminotransferase (ALT)
Time frame: Baseline, Study Completion (about 224 weeks)
Change from Baseline in Body Weight
Time frame: Baseline, Study Completion (about 224 weeks)
Change from Baseline in Non-Alcoholic Steatohepatitis-CHECK Score (NASH-CHECK)
Time frame: Baseline, Week 104
Time to First Occurrence of Any Component Event of the Composite Endpoint of Major Adverse Cardiovascular Events (MACE-3)
MACE-3 composite endpoint includes nonfatal myocardial infarction, nonfatal stroke, cardiovascular death
Time frame: Baseline up to Study Completion (about 224 weeks)
Showing the first 100 of 563 sites across 34 countries. Choose a country and city above to see the rest.
Plan to share: Yes — Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting information: Study protocol, Statistical analysis plan
Time frame: Data are available 6 months after the primary publication or approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Data sharing details ↗ · vivli.org
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drugs tested here: Tirzepatide · Retatrutide
Non-alcoholic Fatty Liver Disease →