Tirzepatide Research for Fatty Liver Disease (MASH)

Tirzepatide has shown promising results for metabolic dysfunction-associated steatohepatitis (MASH) in clinical trials. The phase 2 SYNERGY-NASH trial in 190 randomized adults with biopsy-confirmed MASH and F2-F3 fibrosis reported MASH resolution without fibrosis worsening in 44%-62% across tirzepatide groups versus 10% on placebo at 52 weeks. Fibrosis improvement without MASH worsening was 51%-55% versus 30%, with uncertainty around the smaller between-group differences. This trial did not compare tirzepatide with another GLP-1 agonist or prove which mechanism produced the histologic effect. Its phase 2 histology endpoints do not establish prevention of cirrhosis or liver events. Tirzepatide is not US-approved for MASH. Larger and longer trials are needed to test clinical outcomes and safety in this population.