Bo Xu, Mingxia Yang, Shaoqian Li, Bo Kang, Jiecan Zhou
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We used Mantel-Haenszel statistical method, risk ratio (RR), and 95% confidence interval (CI) to dichotomous variables.</p><p><strong>Results: </strong>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; <i>P</i> = 0.64), cerebrovascular accident (RR = 1.05; 95% CI = 0.91-1.22; <i>P</i> = 0.50), dementia (RR = 1.29; 95% CI = 0.78-2.12; <i>P</i> = 0.32), carotid artery occlusion/carotid artery stenosis (RR = 1.18; 95% CI: 0.92-1.53; <i>P</i> = 0.20), haemorrhagic stroke (RR = 0.84; 95% CI = 0.62-1.12; <i>P</i> = 0.23), and transient ischaemic attack (RR = 0.97; 95% CI = 0.82-1.15; <i>P</i> = 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; <i>P</i> < 0.01) and carotid artery occlusion/carotid artery stenosis (RR = 1.65; 95% CI = 1.04-2.61; <i>P</i> = 0.03), respectively.</p><p><strong>Conclusion and relevance: </strong>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.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"809-821"},"PeriodicalIF":2.3000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Nervous System Disorders: A Systematic Review and Meta-Analysis.\",\"authors\":\"Bo Xu, Mingxia Yang, Shaoqian Li, Bo Kang, Jiecan Zhou\",\"doi\":\"10.1177/10600280251317495\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>This systematic review and meta-analysis aimed to investigate the effects of SGLT2 inhibitors on nervous system disorders.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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; <i>P</i> = 0.64), cerebrovascular accident (RR = 1.05; 95% CI = 0.91-1.22; <i>P</i> = 0.50), dementia (RR = 1.29; 95% CI = 0.78-2.12; <i>P</i> = 0.32), carotid artery occlusion/carotid artery stenosis (RR = 1.18; 95% CI: 0.92-1.53; <i>P</i> = 0.20), haemorrhagic stroke (RR = 0.84; 95% CI = 0.62-1.12; <i>P</i> = 0.23), and transient ischaemic attack (RR = 0.97; 95% CI = 0.82-1.15; <i>P</i> = 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; <i>P</i> < 0.01) and carotid artery occlusion/carotid artery stenosis (RR = 1.65; 95% CI = 1.04-2.61; <i>P</i> = 0.03), respectively.</p><p><strong>Conclusion and relevance: </strong>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.</p>\",\"PeriodicalId\":7933,\"journal\":{\"name\":\"Annals of Pharmacotherapy\",\"volume\":\" \",\"pages\":\"809-821\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Pharmacotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/10600280251317495\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/2/23 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Pharmacotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/10600280251317495","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/23 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
背景：患有2型糖尿病（T2DM）的成年人患某些脑或精神疾病的风险增加，患有或不患有慢性肾脏疾病或心力衰竭的人也是如此。钠-葡萄糖共转运蛋白2 （SGLT2）抑制剂是否与这些疾病相关尚不清楚。目的：本系统综述和荟萃分析旨在探讨SGLT2抑制剂对神经系统疾病的影响。方法：我们检索PubMed、ClinicalTrials.gov和Web of Science，检索至少24周的随机、双盲安慰剂对照试验。我们采用Mantel-Haenszel统计方法，采用风险比（RR）和95%置信区间（CI）对二分类变量进行分析。结果：我们纳入了52篇出版物/试验，涵盖了111 376名受试者(SGLT2抑制剂62 192名；安慰剂49（184）。钠-葡萄糖共转运蛋白2抑制剂对缺血性卒中无显著影响(RR = 0.97；95% ci = 0.87-1.09；P = 0.64)，脑血管意外(RR = 1.05；95% ci = 0.91-1.22；P = 0.50)、痴呆(RR = 1.29；95% ci = 0.78-2.12；P = 0.32)，颈动脉闭塞/颈动脉狭窄(RR = 1.18；95% ci: 0.92-1.53；P = 0.20)，出血性卒中(RR = 0.84；95% ci = 0.62-1.12；P = 0.23)，短暂性缺血发作(RR = 0.97；95% ci = 0.82-1.15；P = 0.73)。未观察到显著的异质性。然而，SGLT2抑制剂在降低帕金森病（主要心力衰竭亚组）的风险方面显示出轻微的作用。恩帕列净和达格列净显著增加晕厥的风险(RR = 1.65；95% ci = 1.15-2.38；P < 0.01)、颈动脉闭塞/颈动脉狭窄(RR = 1.65；95% ci = 1.04-2.61；P = 0.03)。结论及相关性：SGLT2抑制剂对神经系统疾病无显著影响。在一些特定人群中观察到帕金森病的风险降低。此外，恩格列净和达格列净对晕厥和颈动脉闭塞/颈动脉狭窄的风险值得关注。
Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Nervous System Disorders: A Systematic Review and Meta-Analysis.
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.
期刊介绍：
Annals of Pharmacotherapy (AOP) is a peer-reviewed journal that advances pharmacotherapy throughout the world by publishing high-quality research and review articles to achieve the most desired health outcomes.The articles provide cutting-edge information about the most efficient, safe and cost-effective pharmacotherapy for the treatment and prevention of various illnesses. This journal is a member of the Committee on Publication Ethics (COPE). Average time from submission to first decision: 14 days
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