Glucagon-like peptide 1 receptor agonists and venous thromboembolism in type 2 diabetes: a target trial emulation

Feb 5, 2025Blood advances

Glucagon-like peptide 1 receptor agonists and risk of blood clots in veins among people with type 2 diabetes

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Abstract

In a cohort of 540,258 patients, the incidence of venous thromboembolism (VTE) was 6.1 events per 1000 patient-years for those receiving GLP1-receptor agonists compared to 7.6 events for those receiving DPP4 inhibitors.

GLP1-receptor agonist use is associated with a lower incidence of VTE in patients with type 2 diabetes mellitus compared to DPP4 inhibitors.
The hazard ratio for VTE with GLP1-RA was 0.78, indicating a potential reduction in risk.
For pulmonary embolism, the incidence was 2.9 events per 1000 patient-years in the GLP1-RA group versus 3.8 in the DPP4i group, with a hazard ratio of 0.74.
For deep vein thrombosis, GLP1-RA users had 3.9 events per 1000 patient-years compared to 4.7 events per 1000 patient-years in the DPP4i group, with a hazard ratio of 0.81.

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Glucagon-like peptide 1 receptor agonists (GLP1-RA) are antidiabetic agents recently approved for weight loss. Obesity is an established risk factor for venous thromboembolism (VTE). Moreover, preclinical studies have shown that GLP1-RA may attenuate thromboxane-induced platelet activation. Therefore, we hypothesized that GLP1-RA use may reduce the risk of VTE. We performed a target trial emulation (TTE) using a population-based database of electronic health records to evaluate whether GLP1-RA use is associated with a reduction in VTE in patients with type 2 diabetes mellitus (T2DM) compared with dipeptidyl peptidase-4 inhibitors (DPP4i). Patients who were newly initiated on GLP1-RA were propensity score matched to patients who were newly initiated on DPP4i. We evaluated the primary outcome, composite VTE, identified using ICD-10 (International Classification of Diseases, Tenth Revision) codes, within 12 months of the initiation of GLP1-RA or DPP4i. The study cohort comprised 540 258 patients with 270 129 individuals receiving either GLP1-RA or DPP4i. Over 12 months of follow-up, patients who received GLP1-RA had a lower incidence of VTE compared with patients who received DPP4i (6.1 vs 7.6 events per 1000 patient-years; hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.73-0.83). This was similar for pulmonary embolism (2.9 vs 3.8 events per 1000 patient-years; HR, 0.74; 95% CI, 0.68-0.82) and deep vein thrombosis (3.9 vs 4.7 events per 1000 patient-years; HR, 0.81; 95% CI, 0.75-0.88). In this propensity score-matched, TTE study, patients with T2DM who received a GLP1-RA had a lower risk of VTE at 1 year compared with patients who received DPP4i.

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Glucagon-like peptide 1 receptor agonists and venous thromboembolism in type 2 diabetes: a target trial emulation

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