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Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Nervous System Disorders: A Systematic Review and Meta-Analysis

Xu B, Yang M, Li S, Kang B, Zhou J

The Annals of pharmacotherapy, 2025

111 participants · 4 citations

Abstract

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; P = 0.64), cerebrovascular accident (RR = 1.05; 95% CI = 0.91-1.22; P = 0.50), dementia (RR = 1.29; 95% CI = 0.78-2.12; P = 0.32), carotid artery occlusion/carotid artery stenosis (RR = 1.18; 95% CI: 0.92-1.53; P = 0.20), haemorrhagic stroke (RR = 0.84; 95% CI = 0.62-1.12; P = 0.23), and transient ischaemic attack (RR = 0.97; 95% CI = 0.82-1.15; P = 0.73) compared to placebo. No significant heterogeneity was observed. However, SGLT2 inhibitors showed slight effects to reduce the risk of Parkinson's disease (major heart failure subgroup). Empagliflozin and…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 111 participants or records.

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