Effects of Novel Dual GIP and GLP-1 Receptor Agonist, Tirzepatide, on Biomarkers of Non-Alcoholic Steatohepatitis in Patients with T2DM

Objective: To determine the effect of tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, on biomarkers of nonalcoholic steatohepatitis (NASH) and fibrosis in T2DM patients.

Research Design and Methods: T2DM patients 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 intent-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 and 15 mg).

Conclusions: In post-hoc analyses, higher tirzepatide doses significantly decreased NASH-related biomarkers and increased adiponectin in T2DM patients.