Tirzepatide has demonstrated substantial effects on weight reduction and glycemic control, although its effects on cardiovascular risk biomarkers across multiple biological pathways remain under evaluation. A post hoc analysis of the SURMOUNT-1 randomized controlled trial, published in the Journal of the American College of Cardiology, evaluated the association between tirzepatide treatment and changes in biomarkers linked to inflammation, metabolic and hepatic stress, endothelial dysfunction, and hemostasis/thrombosis in adults with obesity.
The analysis included plasma samples collected at baseline, 24 weeks, and 72 weeks from 392 participants who completed treatment with placebo or tirzepatide 5 mg, 10 mg, or 15 mg once weekly. The primary outcome was change in biomarker levels at 72 weeks.
Findings
- Tirzepatide reduced inflammatory biomarkers, including high-sensitivity C-reactive protein, by 36.9%, 46.9%, and 54.6% with the 5-mg, 10-mg, and 15-mg doses, respectively. Interleukin-6 also decreased across all dose groups (all adjusted P<0.05).
- Markers of metabolic and adiposity-related stress improved significantly. Homeostatic model assessment of insulin resistance decreased by 26.4%, 35.5%, and 39.1%, while leptin decreased by 44.4%, 59.3%, and 61.4% across increasing dose levels (all adjusted P<0.05).
- Adiponectin increased by 21.1%, 35.1%, and 47.7% across the 5-mg, 10-mg, and 15-mg dose groups, respectively. Fibroblast growth factor-21 and gamma-glutamyl transferase also decreased significantly.
- Biomarkers of endothelial dysfunction improved. E-selectin decreased by 12.6%, 20.0%, and 26.4% across increasing dose levels, while soluble intercellular adhesion molecule-1 decreased with the 10-mg and 15-mg doses (all adjusted P<0.05).
- Tirzepatide also reduced plasminogen activator inhibitor-1 antigen across all dose groups. No consistent associations were observed for fibrinogen, tissue plasminogen activator antigen, or thrombomodulin.
The findings suggest that tirzepatide treatment was associated with broad improvements in cardiovascular risk biomarkers in adults with obesity. Further studies are needed to determine whether these biomarker changes translate into long-term cardiovascular benefit.
