Subtype-Dependent Reporting of Stroke With SGLT2 Inhibitors: Implications From a Japanese Pharmacovigilance Study.

Abstract

Volume depletion as an adverse events (AE) caused by sodium-glucose cotransporter-2 inhibitors (SGLT2i) because of their diuretic effect may raise the concern about the risk of lacunar stroke; however, an earlier meta-analysis reported no significant increase in the incidence of stroke without clearly distinguishing stroke subtypes. Here, aiming to investigate subtype-wise reporting of stroke potentially related to SGLT2i treatment, we conducted a disproportionality analysis using the Japanese Adverse Drug Event Report database, which contains approximately 500000 cases recorded between April 2004 and March 2019 to detect stroke as AE signals associated with SGLT2i treatment by calculating the reporting odds ratio (ROR). As a result, we identified 532 stroke event reports with the use of SGLT2i. The SGLT2i showed varying degrees of significantly higher reporting (lower 95% ROR > 1) for all ischemic stroke (ROR, 12.7), thrombosis (ROR, 21.7), lacunar infarction (ROR, 48.9), and embolism (ROR, 2.51), but no significantly higher reporting for hemorrhagic stroke. Current pharmacovigilance results showed that the RORs for stroke following SGLT2i use differ greatly depending on the stroke subtypes. It suggests the need for an observational cohort study to be conducted to investigate the incidence of each stroke subtype as the effect of SGLT2i.