(a)International Training Fellow in Endocrinology and Diabetes, Department of Diabetes and Metabolism, Barts Health NHS Trust, London, UK.
Department of Diabetes and Metabolism, Barts and the London School of Medicine and Dentistry, London, UK.
Diabetes Res Clin Pract. 2018 Sep;143:409-419. doi: 10.1016/j.diabres.2018.05.023. Epub 2018 May 26.
Metformin is a lipophilic biguanide which inhibits hepatic gluconeogenesis and improves peripheral utilization of glucose. It is the first line pharmacotherapy for glucose control in patients with Type 2 diabetes due to its safety, efficacy and tolerability. Metformin exhibits pleotropic effects, which may have beneficial effects on a variety of tissues independent of glucose control. A potential anti-tumourigenic effect of metformin may be mediated by its role in activating AMP-kinase, which in turn inhibits mammalian target of rapamycin (mTOR). Non-AMPK dependent protective pathways may include reduction of insulin, insulin-like growth factor-1, leptin, inflammatory pathways and potentiation of adiponectin, all of which may have a role in tumourigenesis. A role in inhibiting cancer stem cells is also postulated. A number of large scale observational and cohort studies suggest metformin is associated with a reduced risk of a number of cancers, although the data is not conclusive. Recent randomised studies reporting use of metformin in treatment of cancer have revealed mixed results, and the results of much larger randomised trials of metformin as an adjuvant therapy in breast and colorectal cancers are awaited.
二甲双胍是一种亲脂性双胍类药物，可抑制肝糖异生并改善外周葡萄糖利用。由于其安全性、疗效和耐受性，它是 2 型糖尿病患者血糖控制的一线药物治疗。二甲双胍具有多种作用，可能对各种独立于血糖控制的组织具有有益作用。二甲双胍的潜在抗肿瘤作用可能与其激活 AMP 激酶的作用有关，而 AMP 激酶又抑制哺乳动物雷帕霉素靶蛋白（mTOR）。非 AMPK 依赖性保护途径可能包括减少胰岛素、胰岛素样生长因子-1、瘦素、炎症途径和增强脂联素，所有这些都可能在肿瘤发生中发挥作用。还推测其在抑制癌症干细胞中的作用。许多大型观察性和队列研究表明，二甲双胍与多种癌症的风险降低有关，尽管数据尚无定论。最近报告二甲双胍用于癌症治疗的随机研究结果喜忧参半，正在等待更大规模的随机试验结果，以评估二甲双胍作为乳腺癌和结直肠癌辅助治疗的疗效。
