BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with substantially increased risk for cardiovascular events, including ischemic stroke. In turn, ischemic stroke represents a leading cause of mortality and long-term disability worldwide. The recent class of glucose-lowering agents is sodium-glucose cotransporter 2 (SGLT-2) inhibitors, which act through inhibition of glucose reabsorption in the kidney, resulting in glucose excretion without stimulating insulin release. Accumulating data suggests that these agents improve multiple risk factors for ischemic stroke except their glucose-lowering effect.OBJECTIVE: In the present review, the pleiotropic actions of SGLT-2 inhibitors are summarized and their potential implications on ischemic stroke prevention are discussed.METHODS: We performed a comprehensive search of the literature in terms of SGLT-2 inhibitors efficacy on ischemic stroke and traditional risk factors of cerebrovascular disease.RESULTS: Several studies consistently showed that SGLT-2 inhibitors reduce blood pressure, induce weight loss, increase high-density lipoprotein cholesterol levels and reduce triglyceride levels. In addition, they improve several emerging cardiovascular risk factors, most notably arterial stiffness, albuminuria and oxidative stress. However, in the only trial that evaluated the effects of these agents on the incidence of ischemic stroke, empagliflozin did not reduce the risk of first or recurrent stroke despite a significant reduction in cardiovascular and all-cause mortality.CONCLUSION: Despite the multiple pleiotropic effects of SGLT-2 inhibitors, these agents do not appear to affect stroke risk. Ongoing large trials with longer follow-up will evaluate whether the pleiotropic effects of this class will translate into benefits in ischemic stroke prevention.