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 dapagliflozin significantly increased the risk of syncope (RR = 1.65; 95% CI = 1.15-2.38; P < 0.01) and carotid artery occlusion/carotid artery stenosis (RR = 1.65; 95% CI = 1.04-2.61; P = 0.03), respectively.
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.
Keywords
Get full access to this article
View all access options for this article.
References
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
