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

Jul 2, 2025Journal of thrombosis and haemostasis : JTH

Glucagon-like peptide 1 receptor drugs and the risk of blood clots in veins: a review and combined analysis of clinical trials

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Abstract

The median incidence of venous thromboembolism (VTE) was 1.1 per 1000 patient-years in the GLP-1 receptor agonist group compared to 2.5 per 1000 patient-years in the placebo group.

There was no statistically significant difference in overall VTE risk between GLP-1 receptor agonist and placebo groups.
GLP-1 receptor agonists were associated with a significantly lower risk of pulmonary embolism.
No significant differences were found in the risk of deep vein thrombosis or VTE at other sites.
The analysis included data from 27 randomized controlled trials involving 84,003 patients.

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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.

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

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