Adem Muna A, Decourt Boris, Sabbagh Marwan N
Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, 350 W. Thomas Rd., Phoenix, AZ 85013, USA.
Department of Pharmacology and Neuroscience, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Biomedicines. 2024 Jan 3;12(1):99. doi: 10.3390/biomedicines12010099.
Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are chronic, progressive disorders affecting the elderly, which fosters global healthcare concern with the growing aging population. Both T2DM and AD have been linked with increasing age, advanced glycosylation end products, obesity, and insulin resistance. Insulin resistance in the periphery is significant in the development of T2DM and it has been posited that insulin resistance in the brain plays a key role in AD pathogenesis, earning AD the name "type 3 diabetes". These clinical and epidemiological links between AD and T2DM have become increasingly pronounced throughout the years, and serve as a means to investigate the effects of antidiabetic therapies in AD, such as metformin, intranasal insulin, incretins, DPP4 inhibitors, PPAR-γ agonists, SGLT2 inhibitors. The majority of these drugs have shown benefit in preclinical trials, and have shown some promising results in clinical trials, with the improvement of cognitive faculties in participants with mild cognitive impairment and AD. In this review, we have summarize the benefits, risks, and conflicting data that currently exist for diabetic drugs being repurposed for the treatment of AD.
2型糖尿病(T2DM)和阿尔茨海默病(AD)是影响老年人的慢性进行性疾病,随着全球人口老龄化加剧,这引发了全球医疗保健领域的关注。T2DM和AD都与年龄增长、晚期糖基化终产物、肥胖和胰岛素抵抗有关。外周胰岛素抵抗在T2DM的发展中起重要作用,并且有人认为大脑中的胰岛素抵抗在AD发病机制中起关键作用,因此AD被称为“3型糖尿病”。多年来,AD和T2DM之间的这些临床和流行病学联系日益明显,并作为一种手段来研究抗糖尿病疗法对AD的影响,如二甲双胍、鼻内胰岛素、肠促胰岛素、二肽基肽酶4(DPP4)抑制剂、过氧化物酶体增殖物激活受体γ(PPAR-γ)激动剂、钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂。这些药物中的大多数在临床前试验中已显示出益处,并且在临床试验中也显示出一些有前景的结果,即改善了轻度认知障碍和AD患者的认知能力。在本综述中,我们总结了目前将糖尿病药物重新用于治疗AD所存在的益处、风险和相互矛盾的数据。