Wuxi School of Medicine, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China; Shanghai Institute of Material Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
Shanghai Institute of Material Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
Biomed Pharmacother. 2018 Oct;106:1227-1235. doi: 10.1016/j.biopha.2018.07.085. Epub 2018 Jul 20.
Type 2 diabetes (T2D) is the most common type of diabetes mellitus and is mainly characterized by insulin resistance, β-cell dysfunction, and elevated hepatic glucose output. Metformin is a first-line antihyperglycemic agent that works mainly by regulating hepatic glucose production and peripheral insulin sensitivity. Metformin has been clinically applied for more than half a century, although the underlying pharmacological mechanisms remain elusive. This current review mainly focused on the development history of metformin and related preclinical studies on structural modification, pharmacological mechanisms for treatment of T2D, toxicology, pharmacokinetics, and pharmaceutics. The pharmacological function of metformin in lowering hyperglycemia suggests that multi-targeting could be an effective strategy for the discovery of new anti-diabetic drugs. A number of discoveries have revealed the pharmacologic mechanisms of metformin; however, precise mechanisms remain unclear. Deeper investigations on the biological features of metformin are expected to provide more rational applications and indications of this evergreen anti-T2D agent, which will in turn help to better understand the complicated pathogenesis of T2D.
2 型糖尿病（T2D）是最常见的糖尿病类型，主要特征为胰岛素抵抗、β细胞功能障碍和肝葡萄糖输出增加。二甲双胍是一种一线抗高血糖药物，主要通过调节肝葡萄糖生成和外周胰岛素敏感性起作用。二甲双胍已经临床应用了半个多世纪，尽管其潜在的药理学机制仍不清楚。本综述主要关注二甲双胍的发展历史以及结构修饰、治疗 T2D 的药理学机制、毒理学、药代动力学和药剂学相关的临床前研究。二甲双胍降低高血糖的药理学功能表明，多靶点可能是发现新型抗糖尿病药物的有效策略。许多发现揭示了二甲双胍的药理学机制；然而，确切的机制仍不清楚。对二甲双胍生物学特性的更深入研究有望为这种常青的抗 T2D 药物提供更合理的应用和适应症，这反过来也有助于更好地理解 T2D 的复杂发病机制。
