Recent evidence indicates that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) may favorably affect the risk of stroke in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease.
This meta-analysis considered data from cardiovascular outcome trials (CVOTs) regarding the effect of SGLT2i treatment on stroke risk in T2DM patients with an emphasis on patients with impaired renal function.
Double-blind randomized trials (RCTs) representing CVOTs were included if they compared SGLT2i add-on therapy with placebo, and reported stroke among primary or secondary endpoints.
Six eligible multicenter RCTs were included. The pooled analysis of 5 RCTs (n = 40,393) showed a neutral effect on the risk of total stroke from treatment with SGLT2i vs. placebo (hazard ratio, HR 0.90, 95% CI: 0.74-1.09, p = 0.29, I = 58%). Subgroup analysis (4 RCTs) involving patients with impaired renal function (n = 17,072) demonstrated a significant benefit in favor of SGLT2i (HR: 0.66, 95% CI: 0.54-0.82, p<0.0001, I = 8%). The pooled analysis of 2 RCTs (n = 14,543) showed a significant reduction in the risk of hemorrhagic stroke in T2DM patients (HR: 0.46, 95% CI: 0.25-0.83, p = 0.01; I = 0). No differences were noticed regarding the risk of ischemic stroke (HR: 0.97, 95% CI: 0.85-1.12, p = 0.69; I = 0), non-fatal stroke (HR: 0.98, 95% CI: 0.83-1.16, p = 0.79, I = 28%), and fatal stroke (HR: 0.77, 95% CI: 0.50-1.17, p = 0.22, I = 0).
Available data suggest that SGLT2i reduce the risk of total stroke in patients with T2DM and impaired renal function. Based on the findings of two RCTs, these drugs may offer a protection against hemorrhagic stroke.

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