BACKGROUND: Adults with type 2 diabetes mellitus (T2DM) are at an increased risk for certain brain or psychiatric disorders, as are those with or without chronic kidney disease or heart failure. Whether sodium-glucose cotransporter 2 (SGLT2) inhibitors are associated with these diseases is unclear. OBJECTIVE: This systematic review and meta-analysis aimed to investigate the effects of SGLT2 inhibitors on nervous system disorders. METHODS: We searched PubMed, ClinicalTrials.gov, and Web of Science for randomized, double-blind placebo-controlled trials of at least ≥24 weeks. We used Mantel-Haenszel statistical method, risk ratio (RR), and 95% confidence interval (CI) to dichotomous variables. RESULTS: We included 52 publications/trials covering 111 376 participants (SGLT2 inhibitors 62 192
Placebo 49 184). Sodium-glucose cotransporter 2 inhibitors had no significant effect on ischaemic stroke (RR = 0.97
95% CI = 0.87-1.09
CONCLUSION AND RELEVANCE: No significant effect of SGLT2 inhibitors on nervous system disorders was observed. There was reduced risk for Parkinson's Disease observed in some specific populations. In addition, the risks of empagliflozin and dapagliflozin concerning syncope and carotid artery occlusion/carotid artery stenosis are worth attention.