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Published on: June 15, 2011

Explore the Causal Effect of SGLT2 Inhibition on Venous Thromboembolism Events: A Drug-Target Mendelian Randomization

Jing Liu1, Zipei Ma1,2, Piaoran Liu1,2

  • 1Department of Cardiology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.

Clinical and Applied Thrombosis/Hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
|May 28, 2026
PubMed

Insights

Sodium-glucose cotransporter 2 (SGLT2) inhibitors do not appear to causally increase the risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). This study supports the thrombotic safety of SGLT2 inhibitors for patients.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Research
  • Metabolic Diseases

Background:

  • Sodium-glucose cotransporter 2 (SGLT2) inhibitors are established antidiabetic drugs with known cardiorenal benefits.
  • The potential causal link between SGLT2 inhibition and venous thromboembolism (VTE) remains unclear, necessitating further investigation.
  • Understanding this association is crucial for comprehensive patient safety assessments of SGLT2 inhibitors.

Purpose of the Study:

  • To investigate the potential causal relationship between SGLT2 inhibition and the risk of VTE, specifically deep vein thrombosis (DVT) and pulmonary embolism (PE).
  • To assess the thrombotic safety profile of SGLT2 inhibitors using genetic and pharmacovigilance data.
  • To provide robust evidence regarding the association between SGLT2 inhibition and VTE events.

Main Methods:

  • Employed a multifaceted approach including drug-target Mendelian randomization (MR) and summary-data-based MR (SMR) using genetic variants for SGLT2 inhibition.
  • Utilized expression quantitative trait loci (eQTLs) from SLC5A2 and glycemic traits as genetic proxies for SGLT2 inhibition.
  • Conducted meta-analyses across multiple genome-wide association study (GWAS) datasets and pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS).

Main Results:

  • Genetically proxied SGLT2 inhibition was robustly associated with a reduced risk of type 2 diabetes.
  • The majority of MR and meta-analysis results showed no consistent causal association between SGLT2 inhibition and VTE, DVT, or PE.
  • FAERS analysis revealed no significant safety signals for PE or DVT associated with SGLT2 inhibitors.

Conclusions:

  • This comprehensive study provides consistent evidence that SGLT2 inhibition is not causally linked to an increased risk of VTE, DVT, or PE.
  • The findings support the established thrombotic safety profile of SGLT2 inhibitors.
  • Further validation in diverse, non-European cohorts is recommended to confirm generalizability.
Keywords:
FAERSdeep vein thrombosismendelian randomizationpulmonary embolismsodium-glucose cotransporter 2 inhibitorsvenous thromboembolism

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