Glucagon-like peptide 1 receptor agonists and risk of venous thromboembolism: a systematic review and meta-analysis of randomized controlled trials

Background Obesity is an established risk factor for venous thromboembolism (VTE). Observational data suggest that glucagon-like peptide 1 receptor agonists (GLP-1RAs) may reduce the risk of VTE. However, the effects of GLP-1RAs on VTE have not been tested in randomized controlled trials (RCTs). Objectives To investigate the impact of GLP-1RAs on VTE risk using data from RCTs. Methods We conducted a systematic review and meta-analysis of placebo-controlled RCTs focusing on GLP-1RA use in patients with type 2 diabetes mellitus (T2DM) or obesity. Five databases were searched from inception to October 2024. The primary outcome was VTE, which was a composite of pulmonary embolism (PE), deep vein thrombosis, and VTE at other sites, and the secondary outcomes were the individual events. Results Twenty-seven RCTs with 84 003 patients were analyzed. The median incidence of VTE was 1.1 and 2.5 per 1000 patient-years in the GLP-1RA and placebo groups, respectively. There was no statistically significant difference in overall VTE risk between GLP-1RA and placebo groups (risk ratio [RR], 0.70; 95% CI, 0.46-1.07). However, GLP-1RAs were associated with a significantly lower risk of PE (RR, 0.60; 95% CI, 0.39-0.94). In contrast, there were no significant differences in the risk of deep vein thrombosis (RR, 1.21; 95% CI, 0.69-2.12) or VTE at other sites (RR, 0.56; 95% CI, 0.25-1.26). Conclusion In this meta-analysis of randomized trials, GLP-1RAs were not associated with a significant reduction in overall VTE risk but were associated with a lower risk of PE among patients with T2DM or obesity.