Association Between Empagliflozin and Risk of Venous Thromboembolism: An Individual Participant Data Meta-Analysis of Randomized Controlled Trials

Venous thromboembolism (VTE) is when a blood clot forms in a vein. Types of VTE include deep vein thrombosis where the clot forms in a deep vein typically in the leg, and pulmonary embolism where a blood clot blocks a blood vessel in the lungs,
VTE is a major cause of illness and death in people with cardiovascular disease and type 2 diabetes (a condition where the hormone insulin does not work properly, leading to high blood glucose (sugar) levels).

Sodium–glucose cotransporter-2 (SGLT2) inhibitors such as empagliflozin are widely prescribed to improve heart and kidney outcomes. They work by blocking a specific protein in the kidneys that reabsorbs glucose back into the bloodstream after filtering it from the blood. By inhibiting this process, excess glucose is excreted from the body in the urine, which helps to lower blood sugar levels and can also reduce blood pressure, promote weight loss, and offer benefits for heart and kidney health.

However, the effect of these medicines on VTE is uncertain. In a recent meta-analysis (where the data from multiple studies are analyzed together), we found that empagliflozin — but not other SGLT2 inhibitors — was associated with a reduced risk of VTE, but this finding was based on summary trial data, rather than individual participant data, and so could not account for patient-level factors. By using individual participant level data from randomized trials of empagliflozin, we aim to confirm whether empagliflozin reduces the risk of VTE, to identify which patient groups might benefit most, and to explore patient or disease factors associated with risk reduction.

Findings from this work could inform future strategies to repurpose empagliflozin for patients with a high risk of thrombosis who also have type 2 diabetes or cardiovascular conditions, helping clinicians better balance cardiovascular and thrombotic (blood clot) risks.