Venous thromboembolism with modern glucose-lowering agents in diabetes: active-comparator evidence beyond placebo-based meta-analyses
Abstract
The influence of newer glucose-lowering agents on venous thromboembolism (VTE) risk has important therapeutic implications. This meta-analysis compared sodium-glucose cotransporter-2 inhibitors (SGLT2-i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) with dipeptidyl peptidase-4 inhibitors (DPP-4i) and evaluated head-to-head SGLT2i versus GLP1-RA comparisons. Eligible studies enrolled adults with diabetes and reported adjusted relative risks for VTE, pulmonary embolism (PE), or deep vein thrombosis (DVT) using new-user cohort, target-trial emulation, nested case-control, or randomized controlled designs. Pooled estimates were derived using inverse-variance meta-analysis on the log scale, with random-effects sensitivity analyses. Six studies met inclusion criteria, all of moderate risk of bias. Compared with DPP-4i, both SGLT2-i (HR 0.72; 95% CI 0.62-0.82) and GLP1-RA (HR 0.78; 95% CI 0.73-0.83) were associated with significantly reduced VTE risk, whereas no difference was observed between SGLT2-i and GLP1-RA (HR 1.02; 95% CI 0.84-1.23). Component analyses were directionally consistent: for PE, SGLT2-i versus DPP-4i HR 0.44 (95% CI 0.30-0.64) and GLP1-RA versus DPP-4i HR 0.74 (95% CI 0.68-0.82); for DVT, SGLT2-i versus DPP-4i HR 0.82 (95% CI 0.68-0.99) and GLP1-RA versus DPP-4i HR 0.81 (95% CI 0.75-0.88). In adults with diabetes, SGLT2-i and GLP1-RA were each associated with a lower risk of VTE compared with DPP-4i, while head-to-head comparisons showed no clear…
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