Effects of Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide on Biomarkers of Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes

Apr 16, 2020Diabetes care

Tirzepatide’s effects on liver disease markers in people with type 2 diabetes

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Abstract

Significant reductions in biomarkers of nonalcoholic steatohepatitis (NASH) were observed with higher doses of tirzepatide in patients with type 2 diabetes mellitus.

Reductions in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significant across all treatment groups except for tirzepatide 10 mg.
Tirzepatide doses of 5, 10, and 15 mg significantly decreased keratin-18 (K-18) levels.
A significant decrease in procollagen III (Pro-C3) was observed with tirzepatide 15 mg.
Tirzepatide 10 mg showed significant reductions in K-18 and Pro-C3 compared to placebo.
Adiponectin levels significantly increased with tirzepatide compared to placebo at doses of 10 and 15 mg.

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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 (< 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). P

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

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Effects of Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide on Biomarkers of Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes

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