Phase 2: Retatrutide in Metabolic Dysfunction-Associated Steatohepatitis (MASH)
NCT05019261 · Eli Lilly
- Phase
- Phase 2
- Enrollment
- 200 participants
- Est. completion
- Completed 2024
- Sponsor
- Eli Lilly
Background
Phase 2 proof-of-concept trial evaluating retatrutide in adults with biopsy-confirmed MASH (metabolic dysfunction-associated steatohepatitis). The glucagon receptor agonism of retatrutide is hypothesized to provide additional hepatic benefit beyond GLP-1/GIP agonism by promoting hepatic fat oxidation and reducing de novo lipogenesis. Results from this trial informed the design of the Phase 3 TRIUMPH-MASH trial.
Key result
Retatrutide produced significant reductions in liver fat by MRI-PDFF and improvements in liver enzymes (ALT, AST) at 24 weeks. Histological data from the biopsy subset showed MASH resolution rates consistent with the drug's weight loss and glucagon receptor-mediated hepatic effects. Full results pending peer-reviewed publication; data informed the TRIUMPH-MASH Phase 3 design.
Primary endpoint
Change in liver fat content by MRI-PDFF from baseline at 24 weeks
Secondary endpoints
- MASH resolution without worsening of fibrosis (liver biopsy subset)
- Change in ALT and AST
- Change in liver stiffness by elastography
- Change in body weight
- Change in HbA1c (in participants with T2D)
Population
Adults with biopsy-confirmed MASH (NASH) and fibrosis stage F1–F3, with or without type 2 diabetes, n=~200
Intervention
Retatrutide 4 mg, 8 mg, or 12 mg SC once weekly vs. placebo; dose escalation over 16 weeks
Inclusion criteria
Adults ≥ 18 years; biopsy-confirmed MASH with NAS ≥ 3 and fibrosis stage F1–F3; ALT > 1.5× ULN; BMI ≥ 25 kg/m²
Exclusion criteria
Cirrhosis (F4 fibrosis); alcohol consumption > 21 units/week (men) or > 14 units/week (women); other causes of liver disease; decompensated liver disease
Trial information sourced from ClinicalTrials.gov and published literature. TryTrutide is not affiliated with Eli Lilly or any trial site. This is not medical advice.