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


Mark L Hartman 1, Arun J Sanyal 2, Rohit Loomba 3 4, Jonathan M Wilson 5, Amir Nikooienejad 5, Ross Bray 5, Chrisanthi A Karanikas 5, Kevin L Duffin 5, Deborah A Robins 5, Axel Haupt 5

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


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: We retrieved 37 trials, including 3301 patients. Average carbohydrate intake in LC diets was 36% of total energy. VLC diets were associated with significant HbA1c reduction at 3 and 6 months, but not at 12 and 24 months. No significant differences in body weight, lipid profile, or blood pressure were found in the long term. Only a minority of trials reported data on renal function, so renal safety could not be assessed. 

Results: Significant reductions from baseline in ALT (all groups), AST, and AST were observed at 26 weeks. Decreases with tirzepatide were significant compared with placebo for K-18 (10 mg) and Pro-C3 (15 mg) Adiponectin significantly increased from baseline with Tirzep atide compared to placebo.


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