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

What Was Tested

In this phase 3 trial, researchers set out to test Retatrutide and Tirzepatide.

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.

It had four arms (groups): Tirzepatide (TZ01) (experimental), Placebo (TZ01) (placebo comparator), Retatrutide (RT01) (experimental) and Placebo (RT01) (placebo comparator).

Participants will receive tirzepatide subcutaneously (SC).

Participants will receive placebo SC.

Participants will receive retatrutide SC.

The registry classes the interventions as drug.

Who Took Part

The registry lists 4500 planned participants were the target.

It was open to people of any sex aged from 18 years with no upper age limit.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Have ELF score of ≥9 and ≤10.8 at screening. Have VCTE LSM ≥10 kilopascal (kPa) and \<20 kPa at screening.

The full record lists 3 inclusion and 6 exclusion criteria; among the exclusions: 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).

How the Study Was Run

The set-up was randomized, parallel-group and single-blind.

Because people in this Retatrutide study were split into groups at random, differences between the groups are less likely to reflect who happened to join each one.

Groups ran in parallel: each of the participants stayed in one arm throughout.

In this single-blind Retatrutide study one party knew the assignments and the other did not.

Those kept unaware of assignments: participant.

It started in 2025-10-15 with completion listed for 2030-08.

It ran at 563 sites in United States (141), Japan (65), China (40), Brazil (26), India (21) and South Korea (20).

Its stated primary purpose is treatment.

What Was Measured

Researchers chose this as the main measure: Time to First Occurrence of Any Component of the Composite Endpoint for Major Adverse Liver Outcomes (MALO) (time frame: Baseline up to Study Completion (about 224 weeks)).

It also tracked 9 secondary outcomes, for example Change from Baseline in Enhanced Liver Fibrosis (ELF) Score, Change from Baseline in Vibration-Controlled Transient Elastography Liver Stiffness Measurement (VCTE LSM), Percent Change from Baseline in Liver Fat Content (LFC), Time to Occurrence of Progression to Cirrhosis, Change from Baseline in Aspartate Aminotransferase (AST) and Change from Baseline in Alanine Aminotransferase (ALT).

What This Means in Plain Language

Put simply, this is a phase 3, randomized trial of Retatrutide and Tirzepatide in 4500 people.

With 4500 participants it is a large trial for this field.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Retatrutide compound page and the Tirzepatide compound page, all human trials.