Tirzepatide and reduced risk of pulmonary embolism and deep vein thrombosis: a multicenter U.S. cohort study. — VialBase Research

Summary

This population-based retrospective cohort study used the TriNetX US Collaborative Network to examine whether tirzepatide, a dual GIP/GLP-1 receptor agonist, is associated with venous thromboembolism in adults with type 2 diabetes and overweight or obesity. Tirzepatide initiators were propensity score matched to patients receiving lifestyle intervention alone (no weight-loss medications), and incident pulmonary embolism, deep vein thrombosis, and superficial vein thrombosis were tracked between 30 days and 12 months after index. Tirzepatide use was associated with substantially lower 12-month risks of both pulmonary embolism and deep vein thrombosis.

Key Findings

• After propensity score matching for demographic, metabolic, and clinical covariates, 235,200 patients were included (117,600 per cohort).
• Pulmonary embolism: RR 0.215 (95% CI 0.185-0.250); HR 0.258 (95% CI 0.222-0.299); log-rank P < 0.001 vs lifestyle intervention alone.
• Deep vein thrombosis: RR 0.303 (95% CI 0.270-0.340); HR 0.361 (95% CI 0.322-0.406); log-rank P < 0.001.
• Superficial vein thrombosis: no statistically significant difference (RR 0.716, 95% CI 0.484-1.060; HR 0.868, 95% CI 0.586-1.286; P = 0.480).
• Findings for pulmonary embolism and deep vein thrombosis remained significant in the 90-day landmark sensitivity analysis.
• In the semaglutide active-comparator analysis, tirzepatide was associated with significantly lower DVT risk; the PE association was significant by risk-ratio but not by Cox regression.

Relevance to Tirzepatide

This is one of the first large real-world evaluations of a thromboembolic signal for tirzepatide, extending its known metabolic and cardiovascular benefits into venous outcomes. The very large matched sample and the consistency of the pulmonary embolism and deep vein thrombosis reductions across primary and 90-day landmark analyses lend weight to the association, though the observational design cannot establish causation and the lifestyle-only comparator may carry residual confounding. Notably, in a head-to-head active-comparator analysis against Semaglutide, tirzepatide retained a significantly lower DVT risk, suggesting a possible advantage of dual GIP/GLP-1 agonism that warrants prospective confirmation.

Citation

Kahkedjian F, Shah J, Kreidieh F. Tirzepatide and reduced risk of pulmonary embolism and deep vein thrombosis: a multicenter U.S. cohort study. Frontiers in endocrinology. 2026. doi:10.3389/fendo.2026.1885961.

See Also

• Parent compound: Tirzepatide
• Semaglutide