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

• Published in: Diabetes care Vol. 43; no. 6; pp. 1352 - 1355
• Main Authors: Hartman, Mark L, Sanyal, Arun J, Loomba, Rohit, Wilson, Jonathan M, Nikooienejad, Amir, Bray, Ross, Karanikas, Chrisanthi A, Duffin, Kevin L, Robins, Deborah A, Haupt, Axel
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.06.2020
• Subjects: Adiponectin; Adult; Agonists; Alanine; Alanine transaminase; Alanine Transaminase - metabolism; Antidiabetics; Aspartate aminotransferase; Aspartate Aminotransferases - metabolism; Biomarkers; Biomarkers - metabolism; Collagen (type III); Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Female; Fibrosis; Gastric Inhibitory Polypeptide - pharmacology; Gastric Inhibitory Polypeptide - therapeutic use; GIP protein; Glucagon; Glucagon-like peptide 1; Glucagon-like peptide 1 receptors; Glucagon-Like Peptide-1 Receptor - agonists; Glucagon-Like Peptides - analogs & derivatives; Glucagon-Like Peptides - therapeutic use; Humans; Immunoglobulin Fc Fragments - therapeutic use; Keratin; Liver Cirrhosis - drug therapy; Liver Cirrhosis - etiology; Liver Cirrhosis - metabolism; Male; Middle Aged; Motivation; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - etiology; Non-alcoholic Fatty Liver Disease - metabolism; Novel Communications in Diabetes; Polypeptides; Procollagen; Receptors; Receptors, Gastrointestinal Hormone - agonists; Recombinant Fusion Proteins - therapeutic use; Research design; Treatment Outcome
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc19-1892

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