Effects of the SGLT2 inhibitor dapagliflozin in early Alzheimer's disease: A randomized controlled trial

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-06-25 DOI:10.1002/alz.70416

Jeffrey M. Burns, Jill K. Morris, Eric D. Vidoni, Heather M. Wilkins, In-Young Choi, Phil Lee, Suzanne L. Hunt, Jonathan D. Mahnken, William M. Brooks, Rebecca J. Lepping, Aditi Gupta, Russell Esterline, Jan Oscarsson, Russell H. Swerdlow

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Abstract

INTRODUCTION

Due to its metabolic effects, dapagliflozin, a sodium-glucose transporter 2 (SGLT2) inhibitor, holds potential as an Alzheimer's disease (AD) therapeutic.

METHODS

We conducted a double-blind, randomized, placebo-controlled, parallel-group, 12-week single-site study to investigate the effect of dapagliflozin in participants with probable AD (Mini-Mental State Examination [MMSE] score 15–26). We planned to enroll 48 participants with 2:1 randomization to 10 mg dapagliflozin once daily (n = 32) versus matching placebo (n = 16). The primary objective was the effect of dapagliflozin on cerebral N-acetylaspartate (NAA). We also assessed safety, glycemic control, body composition, brain metabolism, and cognition.

RESULTS

There was no change in the primary outcome. There were no significant adverse event differences. Hemoglobin A1c, fat mass, and fat-free lean mass decreased; brain glutathione increased; and Stroop Interference test (but not other cognitive test) performance improved.

DISCUSSION

Treated participants manifested metabolic effects observed in clinical studies of other cohorts. In AD, dapagliflozin use may affect the brain.

Highlights

Dapagliflozin did not alter magnetic resonance spectroscopy N-acetylaspartate (primary outcome) in this exploratory Alzheimer's disease (AD) trial.
Dapagliflozin-induced glucose disposal is sufficient to alter systemic metabolism.
AD patients taking dapagliflozin exhibited metabolic effects seen in diabetics.

Abstract Image

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SGLT2抑制剂达格列净对早期阿尔茨海默病的影响：一项随机对照试验

由于其代谢作用，钠-葡萄糖转运蛋白2 （SGLT2）抑制剂达格列净具有治疗阿尔茨海默病（AD）的潜力。方法：我们进行了一项双盲、随机、安慰剂对照、平行组、为期12周的单站点研究，以研究达格列净对可能患有AD （Mini-Mental State Examination [MMSE]评分15-26）的参与者的影响。我们计划招募48名参与者，以2:1的随机分组，每天一次10mg达格列净（n = 32）和匹配安慰剂（n = 16）。主要目的是达格列净对脑n -乙酰天冬氨酸（NAA）的影响。我们还评估了安全性、血糖控制、身体成分、脑代谢和认知。结果：主要结局无变化。两组不良事件无显著差异。糖化血红蛋白、脂肪量和无脂肪瘦质量降低；脑谷胱甘肽增加；Stroop干扰测试（但不包括其他认知测试）的表现有所改善。讨论：在其他队列的临床研究中观察到，接受治疗的参与者表现出代谢作用。在AD患者中，使用达格列净可能会影响大脑。在这项探索性阿尔茨海默病（AD）试验中，达格列净没有改变n -乙酰天冬氨酸（主要结局）的磁共振波谱。达格列净诱导的葡萄糖处理足以改变全身代谢。服用达格列净的AD患者表现出与糖尿病患者相同的代谢作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.