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. 2025 May 27;9(10):2410-2418.
doi: 10.1182/bloodadvances.2025015871.

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

Cho-Han Chiang  1 , Junmin Song  2 , Yu-Cheng Chang  3 , Soravis Osataphan  4 , Yu-Che Lee  5 , Ko-Yun Chang  5 , Kuan-Yu Chi  2 , Cho-Hung Chiang  6 , Anahita Dua  7 , Leslie Lake  8 , Mandy N Lauw  9 , Kenneth A Bauer  10 , Dhruv S Kazi  11 , Rushad Patell  10
Affiliations

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

Cho-Han Chiang et al. Blood Adv. .

Abstract

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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Conflict of interest statement

Conflict-of-interest disclosure: K.A.B. reports consulting fees from Sanofi, outside the submitted work. R.P. reports consulting fees from Merck Research, outside the submitted work. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Flowchart showing patient inclusion.
Figure 2.
Figure 2.
Effect of GLP1-RA on the risk of VTE.
Figure 3.
Figure 3.
Risk of VTE in patients with T2DM receiving GLP-1RA or DPP4i therapy. PY, patient-years.
Figure 4.
Figure 4.
Subgroup and sensitivity analyses evaluating the effect of GLP1-RA on VTE. AC, anticoagulation; Afib, atrial fibrillation; PY, patient-years.
Figure 5.
Figure 5.
Sensitivity analyses comparing GLP1-RA with other antidiabetic medications on VTE. PY, patient-years; SGLT2i, sodium-glucose cotransporter-2 inhibitors; TZD, thiazolidinedione.
See this image and copyright information in PMC

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