State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.
Front Med. 2023 Jun;17(3):388-431. doi: 10.1007/s11684-023-0998-6. Epub 2023 Jul 4.
Metformin has been used for the treatment of type II diabetes mellitus for decades due to its safety, low cost, and outstanding hypoglycemic effect clinically. The mechanisms underlying these benefits are complex and still not fully understood. Inhibition of mitochondrial respiratory-chain complex I is the most described downstream mechanism of metformin, leading to reduced ATP production and activation of AMP-activated protein kinase (AMPK). Meanwhile, many novel targets of metformin have been gradually discovered. In recent years, multiple pre-clinical and clinical studies are committed to extend the indications of metformin in addition to diabetes. Herein, we summarized the benefits of metformin in four types of diseases, including metabolic associated diseases, cancer, aging and age-related diseases, neurological disorders. We comprehensively discussed the pharmacokinetic properties and the mechanisms of action, treatment strategies, the clinical application, the potential risk of metformin in various diseases. This review provides a brief summary of the benefits and concerns of metformin, aiming to interest scientists to consider and explore the common and specific mechanisms and guiding for the further research. Although there have been countless studies of metformin, longitudinal research in each field is still much warranted.
二甲双胍因其安全性、低成本和出色的临床降糖效果，已被用于治疗 2 型糖尿病数十年。其作用机制复杂，尚未完全阐明。抑制线粒体呼吸链复合物 I 是二甲双胍最被描述的下游机制，导致 ATP 生成减少和 AMP 激活的蛋白激酶（AMPK）激活。同时，许多二甲双胍的新靶点已逐渐被发现。近年来，多项临床前和临床研究致力于除糖尿病之外扩展二甲双胍的适应证。在此，我们总结了二甲双胍在代谢相关疾病、癌症、衰老和与年龄相关疾病、神经退行性疾病这四种疾病中的获益。我们全面讨论了二甲双胍的药代动力学特性和作用机制、治疗策略、临床应用以及在各种疾病中潜在的风险。本综述简要总结了二甲双胍的获益和关注点，旨在引起科学家对其共同和特异机制的兴趣，并为进一步的研究提供指导。虽然已有无数关于二甲双胍的研究，但在各个领域仍需要进行纵向研究。
