INTRODUCTIONEmerging 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.METHODSWe 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.RESULTSSemaglutide 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.DISCUSSIONThese 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.

中文翻译：

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索马鲁肽与 2 型糖尿病患者首次诊断为阿尔茨海默病的相关性：使用美国全国真实世界数据进行靶向试验模拟


引言新出现的临床前证据表明，索马鲁肽是一种用于治疗 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），可预防神经退行性和神经炎症。然而，缺乏其预防阿尔茨海默病 （AD） 能力的真实世界证据。方法我们根据 1.16 亿美国患者的全国电子健康记录 （EHR） 数据库进行了模拟靶点试验。通过将 semaglutide 与其他 7 种抗糖尿病药物进行比较，在 1,094,761 名既往未诊断为 AD 的符合条件的 T2DM 患者中模拟了 7 项目标试验。AD 的首次诊断发生在 3 年随访期内，并使用 Cox 比例风险和 Kaplan-Meier 生存分析进行检查。结果塞马鲁肽与首次诊断 AD 的风险显著降低相关，与胰岛素相比最强 （风险比 [HR]，0.33 [95% CI： 0.21 至 0.51]），与其他 GLP-1RA 相比最弱 （HR，0.59 [95% CI： 0.37 至 0.95]）。在肥胖状况、性别和年龄组中也观察到类似的结果。讨论这些发现支持进一步的研究，以评估 semaglutide 在预防 AD 方面的潜力。亮点 与其他抗糖尿病药物（包括其他 GLP-1RAs）相比，Semaglutide 与 T2DM 患者首次诊断 AD 的风险降低 40% 至 70% 相关。索马鲁肽与 AD 相关药物处方显着降低相关。在肥胖状况、性别和年龄组中也观察到类似的减少。我们的研究结果提供了真实世界的证据，支持 semaglutide 在减轻 T2DM 患者 AD 发生和发展方面的潜在临床益处。 这些发现支持进一步的临床试验，以评估 semaglutide 在延缓或预防 AD 方面的潜力。