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 P 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 P 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.