{"title":"钠-葡萄糖共转运蛋白-2抑制剂与亚型特异性痴呆风险：一项多国和多民族队列研究","authors":"Mingyang Sun, Xiaoling Wang, Zhongyuan Lu, Yitian Yang, Shuang Lv, Mengrong Miao, Wan-Ming Chen, Szu-Yuan Wu, Jiaqiang Zhang","doi":"10.1111/dom.16403","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>Type 2 diabetes mellitus (T2DM) significantly increases the risk of dementia, including Alzheimer's disease (AD), vascular dementia (VaD) and mixed dementia. Although sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown potential neuroprotective effects, previous studies were limited by small sample sizes, single-country datasets and a lack of detailed analyses of dementia subtypes.</p><p><strong>Materials and methods: </strong>This retrospective cohort study utilized the TriNetX database, comprising de-identified electronic health records from over 100 million patients across 98 healthcare organizations worldwide. Adults with T2DM initiating treatment with either SGLT2i or dipeptidyl peptidase-4 inhibitors (DPP4i) between November 20, 2004, and November 20, 2024, were included. Propensity score matching (PSM) at a 1:1 ratio ensured balanced baseline characteristics. Primary outcomes included overall dementia and specific dementia subtypes (VaD, AD, other dementias), while secondary outcomes included all-cause mortality.</p><p><strong>Results: </strong>After 1:1 propensity score matching, 278 689 patients per group were analysed. SGLT2i use was associated with a lower incidence of overall dementia (2.9% vs. 6.7%; adjusted hazard ratio [AHR] 0.77, 95% confidence interval [CI], 0.75-0.79) and a lower risk of vascular dementia (AHR 0.80), Alzheimer's disease (AHR 0.82) and other dementias (AHR 0.68). These associations remained consistent across age, sex, baseline glycaemic control and concurrent medication use in subgroup analyses. SGLT2i use was also linked to lower all-cause mortality (4.1% vs. 11.2%; AHR 0.66, 95% CI, 0.65-0.68). Findings were robust across sensitivity and subgroup analyses, supporting the potential neuroprotective effects of SGLT2i.</p><p><strong>Conclusions: </strong>This large-scale observational study suggests that SGLT2i use is associated with lower risks of multiple dementia subtypes and all-cause mortality in patients with T2DM.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4000,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sodium-glucose cotransporter-2 inhibitors and subtype-specific dementia risk: A multinational and multiethnic cohort study.\",\"authors\":\"Mingyang Sun, Xiaoling Wang, Zhongyuan Lu, Yitian Yang, Shuang Lv, Mengrong Miao, Wan-Ming Chen, Szu-Yuan Wu, Jiaqiang Zhang\",\"doi\":\"10.1111/dom.16403\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>Type 2 diabetes mellitus (T2DM) significantly increases the risk of dementia, including Alzheimer's disease (AD), vascular dementia (VaD) and mixed dementia. Although sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown potential neuroprotective effects, previous studies were limited by small sample sizes, single-country datasets and a lack of detailed analyses of dementia subtypes.</p><p><strong>Materials and methods: </strong>This retrospective cohort study utilized the TriNetX database, comprising de-identified electronic health records from over 100 million patients across 98 healthcare organizations worldwide. Adults with T2DM initiating treatment with either SGLT2i or dipeptidyl peptidase-4 inhibitors (DPP4i) between November 20, 2004, and November 20, 2024, were included. Propensity score matching (PSM) at a 1:1 ratio ensured balanced baseline characteristics. Primary outcomes included overall dementia and specific dementia subtypes (VaD, AD, other dementias), while secondary outcomes included all-cause mortality.</p><p><strong>Results: </strong>After 1:1 propensity score matching, 278 689 patients per group were analysed. SGLT2i use was associated with a lower incidence of overall dementia (2.9% vs. 6.7%; adjusted hazard ratio [AHR] 0.77, 95% confidence interval [CI], 0.75-0.79) and a lower risk of vascular dementia (AHR 0.80), Alzheimer's disease (AHR 0.82) and other dementias (AHR 0.68). These associations remained consistent across age, sex, baseline glycaemic control and concurrent medication use in subgroup analyses. SGLT2i use was also linked to lower all-cause mortality (4.1% vs. 11.2%; AHR 0.66, 95% CI, 0.65-0.68). Findings were robust across sensitivity and subgroup analyses, supporting the potential neuroprotective effects of SGLT2i.</p><p><strong>Conclusions: </strong>This large-scale observational study suggests that SGLT2i use is associated with lower risks of multiple dementia subtypes and all-cause mortality in patients with T2DM.</p>\",\"PeriodicalId\":158,\"journal\":{\"name\":\"Diabetes, Obesity & Metabolism\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2025-04-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes, Obesity & Metabolism\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/dom.16403\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes, Obesity & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/dom.16403","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Sodium-glucose cotransporter-2 inhibitors and subtype-specific dementia risk: A multinational and multiethnic cohort study.
Aims: Type 2 diabetes mellitus (T2DM) significantly increases the risk of dementia, including Alzheimer's disease (AD), vascular dementia (VaD) and mixed dementia. Although sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown potential neuroprotective effects, previous studies were limited by small sample sizes, single-country datasets and a lack of detailed analyses of dementia subtypes.
Materials and methods: This retrospective cohort study utilized the TriNetX database, comprising de-identified electronic health records from over 100 million patients across 98 healthcare organizations worldwide. Adults with T2DM initiating treatment with either SGLT2i or dipeptidyl peptidase-4 inhibitors (DPP4i) between November 20, 2004, and November 20, 2024, were included. Propensity score matching (PSM) at a 1:1 ratio ensured balanced baseline characteristics. Primary outcomes included overall dementia and specific dementia subtypes (VaD, AD, other dementias), while secondary outcomes included all-cause mortality.
Results: After 1:1 propensity score matching, 278 689 patients per group were analysed. SGLT2i use was associated with a lower incidence of overall dementia (2.9% vs. 6.7%; adjusted hazard ratio [AHR] 0.77, 95% confidence interval [CI], 0.75-0.79) and a lower risk of vascular dementia (AHR 0.80), Alzheimer's disease (AHR 0.82) and other dementias (AHR 0.68). These associations remained consistent across age, sex, baseline glycaemic control and concurrent medication use in subgroup analyses. SGLT2i use was also linked to lower all-cause mortality (4.1% vs. 11.2%; AHR 0.66, 95% CI, 0.65-0.68). Findings were robust across sensitivity and subgroup analyses, supporting the potential neuroprotective effects of SGLT2i.
Conclusions: This large-scale observational study suggests that SGLT2i use is associated with lower risks of multiple dementia subtypes and all-cause mortality in patients with T2DM.
期刊介绍：
Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
