Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Clearwater, FL, USA.
Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Clearwater, FL, USA.
Life Sci. 2024 Oct 15;355:123001. doi: 10.1016/j.lfs.2024.123001. Epub 2024 Aug 21.
Repurposing antidiabetic drugs for the treatment of Alzheimer's disease (AD) has emerged as a promising therapeutic strategy. This review examines the potential of repurposing antidiabetic drugs for AD treatment, focusing on preclinical evidence, clinical trials, and observational studies. In addition, the review aims to explore challenges and opportunities in repurposing antidiabetic drugs for AD, emphasizing the importance of well-designed clinical trials that consider patient selection criteria, refined outcome measures, adverse effects, and combination therapies to enhance therapeutic efficacy. Preclinical evidence suggests that glucagon-like peptide-1 (GLP-1) analogs, dipeptidyl peptidase-4 (DPP4) inhibitors, metformin, thiazolidinediones, and sodium-glucose co-transporter-2 (SGLT2) inhibitors exhibit neuroprotective effects in AD preclinical models. In preclinical studies, antidiabetic drugs have demonstrated neuroprotective effects by reducing amyloid beta (Aβ) plaques, tau hyperphosphorylation, neuroinflammation, and cognitive impairment. Antidiabetic drug classes, notably GLP-1 analogs and SGLT2 inhibitors, and a reduced risk of dementia in patients with diabetes mellitus. While the evidence for DPP4 inhibitors is mixed, some studies suggest a potential protective effect. On the other hand, alpha-glucosidase inhibitors (AGIs) and sulfonylureas may potentially increase the risk, especially in those experiencing recurrent hypoglycemic events. Repurposing antidiabetic drugs for AD is a promising therapeutic strategy, but challenges such as disease heterogeneity, limited biomarkers, and benefits versus risk evaluation need to be addressed. Ongoing clinical trials in mild cognitive impairment (MCI) and early AD patients without diabetes will be crucial in determining the clinical efficacy and safety of the antidiabetic drugs, paving the way for potential treatments for AD.
将治疗糖尿病的药物重新用于治疗阿尔茨海默病（AD）已成为一种很有前途的治疗策略。本文综述了将治疗糖尿病的药物重新用于 AD 治疗的潜力，重点关注了临床前证据、临床试验和观察性研究。此外，本综述旨在探讨将治疗糖尿病的药物重新用于 AD 的挑战和机遇，强调了设计良好的临床试验的重要性，这些试验需要考虑患者选择标准、细化的结局指标、不良反应以及联合治疗，以提高治疗效果。临床前证据表明，胰高血糖素样肽-1（GLP-1）类似物、二肽基肽酶-4（DPP4）抑制剂、二甲双胍、噻唑烷二酮类和钠-葡萄糖协同转运蛋白-2（SGLT2）抑制剂在 AD 临床前模型中具有神经保护作用。在临床前研究中，抗糖尿病药物通过减少淀粉样蛋白β（Aβ）斑块、tau 过度磷酸化、神经炎症和认知障碍，显示出神经保护作用。抗糖尿病药物类别，特别是 GLP-1 类似物和 SGLT2 抑制剂，与糖尿病患者痴呆风险降低有关。虽然 DPP4 抑制剂的证据存在差异，但一些研究表明其可能具有保护作用。另一方面，α-葡萄糖苷酶抑制剂（AGIs）和磺酰脲类药物可能会增加风险，尤其是在反复发生低血糖事件的患者中。将治疗糖尿病的药物重新用于 AD 是一种很有前途的治疗策略，但需要解决疾病异质性、有限的生物标志物以及获益与风险评估等挑战。正在进行的针对无糖尿病的轻度认知障碍（MCI）和早期 AD 患者的临床试验，对于确定抗糖尿病药物的临床疗效和安全性至关重要，为 AD 的潜在治疗方法铺平了道路。
