GLP-1RA comparative effectiveness against dementia onset relative to other antidiabetic medications in a large, multi-site cohort of patients with type 2 diabetes

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-09-15 DOI:10.1002/alz.70621

Nerissa Nance, Paola Gilsanz, Andrew J. Karter, Holly Finertie, Julie A. Schmittdiel, JaeJin An, Alyce S. Adams, Caryn Oshiro, Andrea E. Cassidy-Bushrow, Sarah Krahe-Dombrowski, Maher Yassin, Sharon Lin, Keanu Izadian, Patrick J. O'Connor, Romain Neugebauer

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Abstract

INTRODUCTION

To address gaps in current research, this study aims to compare the impact of exposure to glucagon-like peptide-1 receptor agonists (GLP-1RA) versus sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase 4 inhibitors (DPP4i), and sulfonylureas (SU) on reducing the risk of dementia, using a rigorous targeted learning causal inference approach.

METHODS

Using clinical and claims data from four diverse US health-care systems, we emulated three two-arm trials contrasting sustained treatment with GLP-1RA versus SGLT2i, DPP4i, and SU on dementia diagnosis. We included diabetes patients aged ≥ 60 years who initiated medication between 2014 and 2022. We estimated cumulative risk differences at 2.5 years.

RESULTS

In Cohort 1, there was no evidence of differential dementia risk between sustained exposure to GLP1-RA versus SGLT2i (adjusted risk difference [aRD] −0.001, 95% confidence interval [CI] −0.004, 0.001). In Cohorts 2 and 3, GLP-1RA was associated with reduced risk of dementia diagnosis compared to DPP4i and SU, respectively (aRD −0.013, 95% CI −0.017, −0.009; aRD −0.016, 95% CI −0.018, −0.015).

DISCUSSION

Rigorous causal inference analysis suggests that sustained exposure to GLP-1RA may modestly reduce risk of dementia, compared to DPP4i or SU exposure—but not compared to SGLT2i.

Highlights

We researched the comparative effects of diabetes medications on dementia.
We studied a large, diverse observational cohort of patients with diabetes in the United States.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) may modestly reduce risk of dementia compared to dipeptidyl peptidase 4 inhibitor or sulfonylurea exposure.
GLP-1RAs do not show evidence of dementia risk reduction compared to sodium-glucose cotransporter 2 inhibitors.
Physicians may consider this when making prescription decisions with patients.

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GLP-1RA在一项大型、多地点2型糖尿病患者队列研究中相对于其他降糖药物对痴呆发病的比较效果

为了解决当前研究中的空白，本研究旨在比较暴露于胰高血糖素样肽-1受体激动剂（GLP-1RA）与钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）、二肽基肽酶4抑制剂（DPP4i）和磺脲类药物（SU）对降低痴呆风险的影响，采用严格的靶向学习因果推理方法。方法使用来自美国四个不同医疗保健系统的临床和索赔数据，我们模拟了三个两组试验，比较GLP-1RA与SGLT2i， DPP4i和SU在痴呆诊断方面的持续治疗。我们纳入了2014年至2022年间开始用药的年龄≥60岁的糖尿病患者。我们估计累积风险差异为2.5年。结果在队列1中，没有证据表明持续暴露于GLP1-RA与SGLT2i之间存在痴呆风险差异（调整风险差[aRD] - 0.001, 95%可信区间[CI] - 0.004, 0.001）。在队列2和3中，与DPP4i和SU相比，GLP-1RA分别与痴呆诊断风险降低相关（aRD - 0.013, 95% CI - 0.017, - 0.009; aRD - 0.016, 95% CI - 0.018, - 0.015）。严格的因果推理分析表明，与DPP4i或SU暴露相比，持续暴露于GLP-1RA可能会适度降低痴呆风险，但与SGLT2i相比则不然。我们研究了糖尿病药物对痴呆的比较效果。我们研究了美国一个大型的、多样化的糖尿病患者观察队列。与二肽基肽酶4抑制剂或磺脲暴露相比，胰高血糖素样肽-1受体激动剂（GLP-1RAs）可适度降低痴呆风险。与钠-葡萄糖共转运蛋白2抑制剂相比，GLP-1RAs没有显示出痴呆风险降低的证据。医生在给病人开处方时可能会考虑到这一点。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.