1. Effects of Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide on Biomarkers of Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes
- Author
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Axel Haupt, Kevin L. Duffin, Mark L. Hartman, Jonathan M. Wilson, Arun J. Sanyal, Chrisanthi A. Karanikas, Deborah A. Robins, Amir Nikooienejad, Rohit Loomba, and Ross Bray
- Subjects
Liver Cirrhosis ,Male ,Endocrinology, Diabetes and Metabolism ,Glucagon-Like Peptides ,Type 2 diabetes ,Medical and Health Sciences ,Hepatitis ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Receptors ,Medicine ,030212 general & internal medicine ,education.field_of_study ,Gastrointestinal Hormone ,Liver Disease ,Diabetes ,Alanine Transaminase ,Middle Aged ,Novel Communications in Diabetes ,Treatment Outcome ,6.1 Pharmaceuticals ,Female ,Type 2 ,medicine.drug ,Agonist ,Adult ,medicine.medical_specialty ,medicine.drug_class ,Recombinant Fusion Proteins ,Population ,Clinical Trials and Supportive Activities ,030209 endocrinology & metabolism ,Gastric Inhibitory Polypeptide ,Glucagon-Like Peptide-1 Receptor ,Receptors, Gastrointestinal Hormone ,03 medical and health sciences ,Endocrinology & Metabolism ,Clinical Research ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,Diabetes Mellitus ,Humans ,Aspartate Aminotransferases ,education ,Glucagon-like peptide 1 receptor ,Metabolic and endocrine ,Advanced and Specialized Nursing ,Adiponectin ,business.industry ,Type 2 Diabetes Mellitus ,Evaluation of treatments and therapeutic interventions ,nutritional and metabolic diseases ,medicine.disease ,Immunoglobulin Fc Fragments ,Endocrinology ,Diabetes Mellitus, Type 2 ,Dulaglutide ,business ,Digestive Diseases ,Biomarkers - Abstract
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 (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, 15 mg). CONCLUSIONS In post hoc analyses, higher tirzepatide doses significantly decreased NASH-related biomarkers and increased adiponectin in patients with T2DM.
- Published
- 2019