Associations of semaglutide with Alzheimer's disease-related dementias in patients with type 2 diabetes: A real-world target trial emulation study

作者：William Yang Wang, Pamela B. Davis, Xin Qi, Mark E. Gurney, George Perry, Nora D. Volkow, David C. Kaelber, Rong Xu · 发表于：Journal of Alzheimer s Disease · 年份：2025 · DOI：10.1177/13872877251351329 · 被引用次数：25 · 研究领域：Diabetes Treatment and Management、Metabolism, Diabetes, and Cancer、Ginkgo biloba and Cashew Applications

Background: Almost half of the dementia cases are preventable. Semaglutide treats several medical conditions that are risk factors for dementia. Objective: We aim to investigate if semaglutide is associated with a decreased risk of dementia. Methods: We conducted emulation target trials based on a nationwide population-based database of patient electronic health records (EHRs) in the US among 1,710,995 eligible patients with type 2 diabetes (T2D) comparing semaglutide with other antidiabetic medications. First-time diagnosis of Alzheimer's disease-related dementia (ADRD) including vascular dementia, frontotemporal dementia, Lewy body dementia and other dementias were examined using Cox proportional hazards and Kaplan-Meier survival analyses during a 3-year follow-up. Models were adjusted by propensity-score matching. Results: We show that semaglutide was associated with a significantly reduced risk of overall ADRD incidence with a hazard ratio ranging from 0.54 (0.49-0.59) compared with insulin, 0.67 (0.61-0.74) compared with metformin, to 0.80 (0.72-0.89) compared with older generation glucagon-like peptide-1 agonists (GLP-1RAs). The association varied for specific dementia types, with significantly reduced risk of vascular dementia and no evidence of associations with frontotemporal and Lewy body dementias. Conclusions: These findings provide evidence supporting protective effects of semaglutide on dementias in patients with T2D. Future works are needed to establish the cau...