Comparative study of SGLT2 inhibitors and metformin: Evaluating first-line therapies for dementia prevention in type 2 diabetes

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism Pub Date : 2025-04-21 DOI:10.1016/j.diabet.2025.101655

Mingyang Sun , Xiaoling Wang , Zhongyuan Lu , Yitian Yang , Shuang Lv , Mengrong Miao , Wan-Ming Chen , Szu-Yuan Wu , Jiaqiang Zhang

{"title":"Comparative study of SGLT2 inhibitors and metformin: Evaluating first-line therapies for dementia prevention in type 2 diabetes","authors":"Mingyang Sun , Xiaoling Wang , Zhongyuan Lu , Yitian Yang , Shuang Lv , Mengrong Miao , Wan-Ming Chen , Szu-Yuan Wu , Jiaqiang Zhang","doi":"10.1016/j.diabet.2025.101655","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div><em>-</em> Type 2 diabetes (T2D) increases the risk of dementia by 1.5 to 2.5 times. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and metformin, widely used antidiabetic therapies, have demonstrated potential neuroprotective effects. Their comparative effectiveness in dementia prevention remains unknown.</div></div><div><h3>Methods</h3><div><em>-</em> This retrospective cohort study used the TriNetX global federated network, analyzing de-identified records from over 98 healthcare organizations. Adults with T2D initiating SGLT2i or metformin as first-line therapy were propensity score-matched (1:1). The primary outcome was overall dementia incidence, including vascular dementia, Alzheimer’s disease, and other subtypes. Secondary outcomes included all-cause mortality. Time-to-event outcomes were assessed using Kaplan-Meier curves and Cox models.</div></div><div><h3>Results</h3><div><em>-</em> Among 74,975 matched patients in each cohort, SGLT2i use was associated with a lower incidence of overall dementia: 2.7 % vs. 6.9 %: adjusted hazard ratio (aHR) 0.80 [95 % CI 0.76;0.84]. Reductions were observed in vascular dementia (0.8 % vs. 2.0 %; aHR 0.87), Alzheimer’s dementia (1.1 % vs. 3.2 %; aHR, 0.76), and all-cause mortality (6.8 % vs. 15.4 %; aHR, 0.92). Benefits were pronounced in older adults, particularly those aged ≥80 years.</div></div><div><h3>Conclusions</h3><div><em>-</em> SGLT2is significantly reduced dementia risk and mortality compared to metformin in T2D patients. These findings suggest SGLT2is may offer superior neuroprotective benefits, underscoring their potential as a first-line therapy for T2D. Further randomized trials are needed to confirm these results.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 4","pages":"Article 101655"},"PeriodicalIF":4.6000,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes & metabolism","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1262363625000503","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Background

- Type 2 diabetes (T2D) increases the risk of dementia by 1.5 to 2.5 times. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and metformin, widely used antidiabetic therapies, have demonstrated potential neuroprotective effects. Their comparative effectiveness in dementia prevention remains unknown.

Methods

- This retrospective cohort study used the TriNetX global federated network, analyzing de-identified records from over 98 healthcare organizations. Adults with T2D initiating SGLT2i or metformin as first-line therapy were propensity score-matched (1:1). The primary outcome was overall dementia incidence, including vascular dementia, Alzheimer’s disease, and other subtypes. Secondary outcomes included all-cause mortality. Time-to-event outcomes were assessed using Kaplan-Meier curves and Cox models.

Results

- Among 74,975 matched patients in each cohort, SGLT2i use was associated with a lower incidence of overall dementia: 2.7 % vs. 6.9 %: adjusted hazard ratio (aHR) 0.80 [95 % CI 0.76;0.84]. Reductions were observed in vascular dementia (0.8 % vs. 2.0 %; aHR 0.87), Alzheimer’s dementia (1.1 % vs. 3.2 %; aHR, 0.76), and all-cause mortality (6.8 % vs. 15.4 %; aHR, 0.92). Benefits were pronounced in older adults, particularly those aged ≥80 years.

Conclusions

- SGLT2is significantly reduced dementia risk and mortality compared to metformin in T2D patients. These findings suggest SGLT2is may offer superior neuroprotective benefits, underscoring their potential as a first-line therapy for T2D. Further randomized trials are needed to confirm these results.

查看原文本刊更多论文

SGLT2抑制剂和二甲双胍的比较研究：评价预防2型糖尿病痴呆的一线疗法

背景- 2型糖尿病（T2D）使痴呆的风险增加1.5至2.5倍。钠-葡萄糖共转运蛋白2抑制剂（SGLT2is）和二甲双胍，广泛应用于降糖治疗，已显示出潜在的神经保护作用。它们在预防痴呆症方面的相对有效性尚不清楚。方法：这项回顾性队列研究使用TriNetX全球联合网络，分析了来自98个医疗保健组织的去识别记录。成人t2dm患者采用SGLT2i或二甲双胍作为一线治疗，倾向评分匹配（1:1）。主要结局是总体痴呆发病率，包括血管性痴呆、阿尔茨海默病和其他亚型。次要结局包括全因死亡率。使用Kaplan-Meier曲线和Cox模型评估事件发生时间。结果：在每个队列的74,975名匹配的患者中，SGLT2i的使用与较低的总体痴呆发病率相关：2.7% vs. 6.9%：校正风险比（aHR） 0.80 [95% CI 0.76;0.84]。血管性痴呆减少(0.8% vs. 2.0%；aHR 0.87)，阿尔茨海默氏痴呆(1.1%对3.2%；aHR, 0.76)和全因死亡率(6.8% vs. 15.4%；aHR, 0.92)。在老年人中获益明显，尤其是年龄≥80岁的老年人。结论：与二甲双胍相比，sglt2dm可显著降低T2D患者的痴呆风险和死亡率。这些发现表明SGLT2is可能具有更好的神经保护作用，强调了它们作为T2D一线治疗的潜力。需要进一步的随机试验来证实这些结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Diabetes & metabolism 医学-内分泌学与代谢

CiteScore

12.00

自引率

4.20%

发文量

审稿时长

13 days

期刊介绍： A high quality scientific journal with an international readership Official publication of the SFD, Diabetes & Metabolism, publishes high-quality papers by leading teams, forming a close link between hospital and research units. Diabetes & Metabolism is published in English language and is indexed in all major databases with its impact factor constantly progressing. Diabetes & Metabolism contains original articles, short reports and comprehensive reviews.