Abstract
Type 2 diabetes mellitus (T2DM) significantly elevates the risk of stroke, a leading cause of global morbidity and mortality. This narrative review synthesizes current evidence on the cerebrovascular effects of antidiabetic agents, focusing on stroke risk modulation, neuroprotection, and post-stroke outcomes. Metformin demonstrates consistent benefits, including reduced stroke incidence (53.2% risk reduction in Asian cohorts) and improved functional recovery, likely mediated by AMPK activation and anti-inflammatory effects. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors show promise in reducing major adverse cardiovascular events (MACE), though their direct impact on stroke remains less defined. Thiazolidinediones (TZDs), particularly pioglitazone, exhibit dose-dependent stroke prevention, especially in high-risk populations, while glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may lower stroke risk via pleiotropic mechanisms. Dipeptidyl peptidase-4 (DPP-4) inhibitors appear neutral, whereas sulfonylureas present conflicting data, with some studies suggesting neuroprotective effects post-stroke. Combination therapies, such as metformin with SGLT-2 inhibitors or GLP-1 RAs, may optimize outcomes but require further validation. Limitations include heterogeneity across studies, unadjusted confounders, and a lack of long-term data. Personalized approaches, considering comorbidities like atrial fibrillation or chronic kidney disease, are emphasized. Future research should prioritize randomized trials with stroke-specific endpoints to clarify therapeutic hierarchies.