Histologic improvements in metabolic dysfunction–associated steatohepatitis (MASH) are associated with weight loss and improved glycemic control in patients treated with tirzepatide. These findings were reported in a post hoc analysis of the SYNERGY-NASH trial, published in Diabetes Care.

The analysis included 154 participants who completed 52 weeks of treatment with once-weekly tirzepatide (5, 10, or 15 mg) or placebo. At baseline, 59% had type 2 diabetes and mean body mass index was 35.7 kg/m².

Participants who achieved MASH resolution or fibrosis improvement experienced greater body weight reductions (−16.0% vs. −7.0% for MASH resolution; −13.6% vs. −9.8% for fibrosis improvement) and larger HbA1c decreases (−1.2% vs. −0.6% and −1.2% vs. −0.7%, respectively) than nonresponders.
MASH responders also showed greater reductions in liver fat and improvements in adipose tissue insulin sensitivity. Causal mediation analysis indicated liver fat normalization significantly contributed to both MASH resolution and fibrosis improvement.

These results suggest tirzepatide’s metabolic effects, including weight loss and improved glycemic control, may play a key role in disease modification for patients with MASH