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

BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist used in patients with type 2 diabetes and obesity. Although tirzepatide improves metabolic and cardiovascular risk factors, its association with venous thromboembolism, including pulmonary embolism and deep vein thrombosis, remains insufficiently characterized in real-world populations. METHODS: We conducted a population-based retrospective cohort study using the TriNetX US Collaborative Network. Adults with type 2 diabetes and overweight or obesity who initiated tirzepatide were propensity score matched to patients receiving lifestyle intervention alone with no exposure to weight-loss medications. Outcomes included incident pulmonary embolism, deep vein thrombosis, and superficial vein thrombosis occurring between 30 days and 12 months after index. Additional analyses included a 90-day landmark sensitivity analysis and an active comparator analysis comparing tirzepatide with semaglutide. RESULTS: After propensity score matching for demographic, metabolic, and clinical covariates, 235, 200 patients were included in the primary analysis (117, 600 per cohort). Tirzepatide use was associated with a significantly lower 12-month risk of pulmonary embolism compared with lifestyle intervention alone (RR, 0.215; 95% CI, 0.185-0.250; HR, 0.258; 95% CI, 0.222-0.299; log-rank  < 0.001). Similar reductions were observed for deep vein thrombosis (RR, 0.303; 95% CI, 0.270-0.340; HR, 0.361; 95% CI, 0.322-0.406; log-rank  < 0.001). No statistically significant difference was observed for superficial vein thrombosis (RR, 0.716; 95% CI, 0.484-1.060; HR, 0.868; 95% CI, 0.586-1.286; log-rank P = 0.480). Findings for pulmonary embolism and deep vein thrombosis remained significant in the 90-day landmark analysis. In the semaglutide comparator analysis, tirzepatide was associated with a significantly lower risk of deep vein thrombosis, while the pulmonary embolism association was significant by risk-ratio analysis but not by Cox regression. CONCLUSIONS: In this large multicenter cohort study, tirzepatide use was associated with a lower risk of pulmonary embolism and deep vein thrombosis compared with lifestyle intervention alone. These findings suggest a potential association between tirzepatide use and lower observed rates of thromboembolic events in patients with diabetes and obesity.