The Effect of Sodium-Glucose Transporter 2 Inhibitors on Stroke in Patients With Type 2 Diabetes: A Meta-analysis

Abstract

Objectives: To provide an update on the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on stroke in patients with type 2 diabetes (T2D).

Methods: PubMed, Embase, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) comparing SGLT2 inhibitors versus placebo or other therapies in patients with T2D and reporting stroke endpoint. We computed the risk ratios (RRs) to binary endpoints, with 95% confidence intervals (CIs).

Results: A total of 71 RCTs and 105,914 patients were included, of whom 62,488 (59%) were randomized to the SGLT2 inhibitors group. The follow-up ranged from 12 weeks to 4.2 years. There were no significant differences between groups in all types of stroke (RR 0.96; 95% CI 0.89-1.04), ischemic stroke (RR 0.89; 95% CI 0.76-1.04), and transient ischemic attack (RR 0.96; 95% CI 0.79-1.16). Patients on SGLT2 inhibitors experienced lower rates of hemorrhagic stroke (RR 0.62; 95% CI 0.39-0.98). In the subgroup analysis of the type of drug, sotagliflozin significantly reduced all types of stroke (RR 0.74; 95% CI 0.56-0.97).

Conclusion: In this meta-analysis of 71 RCTs comprising 105,914 patients with T2D, SGLT2 inhibitors were not associated with a reduced risk of stroke and transient ischemic attack compared to placebo or other therapies; however, there was a trend toward reduced risk of hemorrhagic stroke. Among all SGLT2 inhibitors, sotagliflozin significantly reduced the risk of stroke.

Keywords: Cerebrovascular accident; Sodium-Glucose Transporter 2 Inhibitors; Stroke; Type 2 diabetes.