The Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Cardiovascular Risk Biomarkers in Patients with Type 2 Diabetes: a Post-Hoc Analysis

In a phase 2 trial of once-weekly tirzepatide (1, 5, 10, or 15 mg), dulaglutide (1.5 mg), or placebo, the dual GIP and GLP-1 receptor agonist tirzepatide dose-dependently reduced HbA1c and body weight in patients with type 2 diabetes. In this post-hoc analysis, inflammation, endothelial dysfunction, and cellular stress biomarkers were measured at baseline, 4, 12, and 26 weeks to evaluate additional effects of tirzepatide on cardiovascular risk factors. At 26 weeks, tirzepatide 10 mg and 15 mg decreased YKL-40, ICAM-1, leptin, and GDF-15 levels versus baseline, and YKL-40 and leptin levels versus placebo and dulaglutide. Tirzepatide 15 mg also decreased ICAM-1 levels versus placebo and dulaglutide, and hsCRP levels versus baseline and placebo, but not dulaglutide. GlycA, IL-6, VCAM-1, and NT-proBNP levels were not significantly changed in any group. YKL-40, hsCRP, and ICAM-1 levels rapidly decreased within 4 weeks of treatment with tirzepatide 10 mg and 15 mg, whereas the decrease in leptin levels was more gradual and did not plateau by 26 weeks. In this hypothesis-generating exploratory analysis, tirzepatide decreased several biomarkers that have been associated with cardiovascular risk. This article is protected by copyright. All rights reserved.