Associations of semaglutide with first-time diagnosis of Alzheimer's disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2024-10-24 DOI:10.1002/alz.14313

William Wang, QuangQiu Wang, Xin Qi, Mark Gurney, George Perry, Nora D. Volkow, Pamela B. Davis, David C. Kaelber, Rong Xu

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引用次数: 0

Abstract

INTRODUCTION

Emerging preclinical evidence suggests that semaglutide, a glucagon-like peptide receptor agonist (GLP-1RA) for type 2 diabetes mellitus (T2DM) and obesity, protects against neurodegeneration and neuroinflammation. However, real-world evidence for its ability to protect against Alzheimer's disease (AD) is lacking.

METHODS

We conducted emulation target trials based on a nationwide database of electronic health records (EHRs) of 116 million US patients. Seven target trials were emulated among 1,094,761 eligible patients with T2DM who had no prior AD diagnosis by comparing semaglutide with seven other antidiabetic medications. First-ever diagnosis of AD occurred within a 3-year follow-up period and was examined using Cox proportional hazards and Kaplan–Meier survival analyses.

RESULTS

Semaglutide was associated with significantly reduced risk for first-time AD diagnosis, most strongly compared with insulin (hazard ratio [HR], 0.33 [95% CI: 0.21 to 0.51]) and most weakly compared with other GLP-1RAs (HR, 0.59 [95% CI: 0.37 to 0.95]). Similar results were seen across obesity status, gender, and age groups.

DISCUSSION

These findings support further studies to assess semaglutide's potential in preventing AD.

Highlights

Semaglutide was associated with 40% to 70% reduced risks of first-time AD diagnosis in T2DM patients compared to other antidiabetic medications, including other GLP-1RAs.
Semaglutide was associated with significantly lower AD-related medication prescriptions.
Similar reductions were seen across obesity status, gender, and age groups.
Our findings provide real-world evidence supporting the potential clinical benefits of semaglutide in mitigating AD initiation and development in patients with T2DM.
These findings support further clinical trials to assess semaglutide's potential in delaying or preventing AD.

Abstract Image

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semaglutide与2型糖尿病患者首次诊断阿尔茨海默病的关系：利用美国全国范围内的真实数据模拟目标试验

简介：新近的临床前证据表明，用于治疗2型糖尿病（T2DM）和肥胖症的胰高血糖素样肽受体激动剂（GLP-1RA）--司马鲁肽可防止神经变性和神经炎症。方法我们根据 1.16 亿美国患者的全国电子健康记录 (EHR) 数据库进行了仿真目标试验。我们在 1,094,761 名符合条件的 T2DM 患者中模拟了七项目标试验，这些患者既往未确诊过注意力缺失症，我们将塞马鲁肽与其他七种抗糖尿病药物进行了比较。结果与胰岛素相比，semaglutide能显著降低首次诊断AD的风险（危险比[HR]，0.33 [95% CI：0.21~0.51]），与其他GLP-1RAs相比（HR，0.59 [95% CI：0.37~0.95]），semaglutide的相关性最弱。与其他抗糖尿病药物（包括其他GLP-1RAs）相比，塞马鲁肽可将T2DM患者首次确诊AD的风险降低40%至70%。塞马鲁肽可显著降低AD相关药物的处方量。不同肥胖状况、性别和年龄组的患者的用药量也有类似的减少。我们的研究结果提供了真实世界的证据，支持塞马鲁肽在减轻T2DM患者AD诱发和发展方面的潜在临床益处。这些发现支持进一步开展临床试验，以评估塞马鲁肽在延缓或预防注意力缺失症方面的潜力。

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.