OBJECTIVE: To determine the effect of tirzepatide, a dual agonist of 
glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 
receptors, on biomarkers of nonalcoholic steatohepatitis (NASH) and fibrosis in 
patients with type 2 diabetes mellitus (T2DM).
RESEARCH DESIGN AND METHODS: Patients with T2DM received either once weekly 
tirzepatide (1, 5, 10, or 15 mg), dulaglutide (1.5 mg), or placebo for 26 weeks. 
Changes from baseline in alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), keratin-18 (K-18), procollagen III (Pro-C3), and 
adiponectin were analyzed in a modified intention-to-treat population.
RESULTS: Significant (P < 0.05) reductions from baseline in ALT (all groups), 
AST (all groups except tirzepatide 10 mg), K-18 (tirzepatide 5, 10, 15 mg), and 
Pro-C3 (tirzepatide 15 mg) were observed at 26 weeks. Decreases with tirzepatide 
were significant compared with placebo for K-18 (10 mg) and Pro-C3 (15 mg) and 
with dulaglutide for ALT (10, 15 mg). Adiponectin significantly increased from 
baseline with tirzepatide compared with placebo (10, 15 mg).
CONCLUSIONS: In post hoc analyses, higher tirzepatide doses significantly 
decreased NASH-related biomarkers and increased adiponectin in patients with 
T2DM.