134-OR: Effects of Tirzepatide (TZP), a Novel Dual GIP and GLP-1 Receptor Agonist, on Biomarkers of Nonalcoholic Steatohepatitis (NASH) in Patients with T2D

Abstract

Nonalcoholic fatty liver disease (NAFLD) is common in T2D patients and increases the risk of NASH and cirrhosis. In a Phase 2 trial, TZP significantly reduced HbA1c and body weight at 26 weeks (≥ 37% achieved 10% weight loss at 2 highest doses). Patients with T2D were randomly assigned (1:1:1:1:1:1) to receive either once-weekly sc TZP (1, 5, 10, or 15 mg), dulaglutide (1.5 mg), or placebo for 26 weeks. Because of the overlap of T2D and NAFLD populations, we measured several NASH related biomarkers to explore whether TZP may have potential efficacy in NASH. These included: ALT, AST, Keratin-18 M30 fragment (K-18, apoptosis marker; Peviva), Pro-C3 (fibrosis marker, a fragment of the NH₂-terminal propeptide of type III procollagen; Nordic Bioscience), and adiponectin (adipokine that protects liver from inflammation and fibrosis; Pacific Biomarkers). Results (Table) were analyzed in a modified intent-to-treat population using a mixed model for repeated measures. Significant (p<0.05) decreases from baseline with TZP occurred in ALT (all doses), AST (1, 5, 15 mg), K-18 (5, 10, 15 mg) and Pro-C3 (15 mg); decreases were significant for TZP vs. placebo in K-18 (10 mg) and Pro-C3 (15 mg), and for TZP vs. dulaglutide in ALT (10, 15 mg). Increases in adiponectin with TZP were significant compared to placebo for 10 and 15 mg. Further evaluation of TZP in patients with NASH is warranted.

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