| アブストラクト | BackgroundSodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used antidiabetic agents with established cardiorenal benefits, yet their genetic causal association with venous thromboembolism (VTE) remains uncertain.MethodsWe employed a multifaceted approach to investigate the causal relationship between SGLT2 inhibition and VTE, as well as deep vein thrombosis (DVT) and pulmonary embolism (PE). Drug-target Mendelian randomization (MR) and summary-data-based MR (SMR) analyses were conducted using genetic variants proxying SGLT2 inhibition, derived from SLC5A2 expression quantitative trait loci and glycemic traits. Positive control analyses confirmed validity using type 2 diabetes outcomes. Meta-analyses were performed across multiple independent genome-wide association study datasets. Complementary pharmacovigilance analysis was conducted using the FDA Adverse Event Reporting System (FAERS) to assess disproportionality of SGLT2 inhibitor-related VTE reports.ResultsGenetically proxied SGLT2 inhibition was significantly associated with reduced risk of type 2 diabetes (P < 0.05), validating its robustness. Most MR analyses showed no consistent causal association with VTE, DVT, or PE across datasets, and meta-analyses yielded non-significant pooled estimates (all P > 0.05). SMR analyses revealed no association between SLC5A2 expression and VTE-related outcomes (all P_SMR > 0.05). FAERS disproportionality analysis also identified no safety signals for PE (reporting odds ratio [ROR] = 0.51; 95% CI: 0.42-0.64) or DVT (ROR = 0.54; 95% CI: 0.45-0.64).ConclusionsThis integrative study provides consistent evidence that SGLT2 inhibition is not causally associated with VTE, DVT, or PE, supporting its thrombotic safety. However, generalizability to non-European populations requires future validation in diverse cohorts. |
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| ジャーナル名 | Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis |
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| Pubmed追加日 | 2026/5/28 |
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| 投稿者 | Liu, Jing; Ma, Zipei; Liu, Piaoran; Yao, Tiezhu; He, Jing; Wang, Tenghui; Li, Mengjia; Liu, Sihan; Ma, Jingtao; Li, Zhenli |
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| 組織名 | Department of Cardiology, the Fourth Hospital of Hebei Medical University,;Shijiazhuang, Hebei, People's Republic of China.;Graduate School, Hebei Medical University, Shijiazhuang, Hebei, People's Republic;of China. RINGGOLD: 12553;Department of Cardiology, Anzhen Hospital Affiliated to Capital Medical;University, Beijing, People's Republic of China. RINGGOLD: RinggoldId: 12667;Department of Immuno-Oncology, The Fourth Hospital of Hebei Medical University, |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/42206520/ |
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