T2DM patients with incident stroke have a higher risk of mortality than those with diabetes alone 2. Type 2 diabetes mellitus (T2DM) is a highly prevalent disease associated with an increased risk of macrovascular complications (such as acute myocardial infarction and stroke), accounting for 80% of deaths in diabetic individuals 1. This meta-analysis shows that SGLT2 inhibitors have a neutral effect on the risk of stroke and its subtypes but a potential protective effect against hemorrhagic stroke. When only hemorrhagic stroke was included, SGLT2 inhibitors were associated with a significant 50% reduction compared with placebo (RR = 0.49, 95% CI 0.30–0.82, P = 0.007). Subgroup analysis indicated that SGLT2 inhibitors had no significant effect against fatal stroke, non-fatal stroke, ischemic stroke or transient ischemic attack. Pooled analysis of the RCTs showed no significant effect of SGLT2 inhibitors on total stroke. Five eligible RCTs (EMPA-REG, CANVAS, DECLARE-TIMI 58, CREDENCE and VERTIS CV) involving 46,969 participants were included.
![comprehensive meta analysis subgroups comprehensive meta analysis subgroups](https://www.ahajournals.org/cms/asset/96fa38bc-18d9-4e80-b656-e1b48ba9bd48/e172fig02.jpeg)
All data from prospective RCTs up to 20 October 2020 involving SGLT2 inhibitors that reported stroke events as the primary endpoint or safety in subjects with type 2 diabetes were subjected to meta-analysis. The purpose of this study was to perform a meta-analysis to evaluate the effect of SGLT2 inhibitors on the risk of stroke and its subtypes. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown impressive effects in reducing major vascular events in several randomized controlled trials (RCTs).