In a phase 2 trial of once-weekly tirzepatide (1, 5, 10, or 15 mg), dulaglutide 
(1.5 mg), or placebo, the dual glucose-dependent insulinotropic polypeptide and 
glucagon-like peptide-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 the additional 
effects of tirzepatide on cardiovascular risk factors. At 26 weeks, tirzepatide 
10 and 15 mg decreased YKL-40 (also known as chitinase-3 like-protein-1), 
intercellular adhesion molecule 1 (ICAM-1), leptin, and growth differentiation 
factor 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 high-sensitivity C-reactive protein (hsCRP) levels versus 
baseline and placebo, but not dulaglutide. GlycA, interleukin 6, vascular cell 
adhesion molecule 1, and N-terminal-pro hormone B-type natriuretic peptide 
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 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.