Metformin pathways: pharmacokinetics and pharmacodynamics.
Metformin pathways: pharmacokinetics and pharmacodynamics.
复制标题
DOI：
10.1097/fpc.0b013e3283559b22
复制
发表时间：
2012-11
影响因子：
2.6
通讯作者：
Klein TE
中科院分区：
文献类型：
--
作者：
Gong L;Goswami S;Giacomini KM;Altman RB;Klein TE
背景二甲双胍是治疗2型糖尿病(T2 DM，原名非胰岛素依赖型糖尿病)的一线药物，是全球最常用的处方药之一。作为一种双胍类药物，二甲双胍可降低基础和餐后血糖(PPG)1，2。它可以作为单药或与其他抗糖尿病药物联合使用，包括磺脲类药物、α-葡萄糖苷酶抑制剂、胰岛素、噻唑烷二酮类、DPP4抑制剂以及GLP1激动剂。二甲双胍的作用机制是抑制肝脏葡萄糖的产生，减少肠道葡萄糖的吸收，促进葡萄糖的吸收和利用。3.随着美国肥胖症患病率的增加，二甲双胍的使用量也在增加。二甲双胍还可用于其他适应症，如多囊卵巢综合征(PCOS)1。大多数患者对二甲双胍的耐受性良好。然而，二甲双胍对血糖的反应是非常不同的。一些患者的反应非常好，而另一些患者则没有任何益处。4.本综述简要回顾了二甲双胍的药代动力学(图1)，并重点介绍了介导二甲双胍治疗的不同药理反应的基因(图2)。对这些途径的了解可能有助于识别预测反应变异的遗传标记，并有助于二甲双胍治疗的定制。
BackgroundMetformin is a first-line therapy for type 2 diabetes mellitus (T2DM, formerly ‘non-insulin-dependent diabetes mellitus’), and is one of the most commonly prescribed drugs worldwide. As a biguanide agent, metformin lowers both basal and postprandial plasma glucose (PPG) 1, 2. It can be used as a monotherapy or in combination with other antidiabetic agents including sulfonylureas, α-glucosidase inhibitors, insulin, thiazolidinediones, DPP-4 inhibitors as well as GLP-1 agonists. Metformin works by inhibiting the production of hepatic glucose, reducing intestinal glucose absorption, and improving glucose uptake and utilization. Besides lowering the blood glucose level, metformin may have additional health benefits, including weight reduction, lowering plasma lipid levels, and prevention of some vascular complications 3. As the prevalence of obesity in the USA increases, the use of metformin is also increasing. Metformin is also used for other indications such as polycystic ovary syndrome (PCOS) 1. Metformin is well tolerated by the majority of patients. However, the glycemic response to metformin is quite variable. Some patients respond extremely well, whereas others show no benefit 4. This summary briefly reviews the pharmacokinetics of metformin (Fig. 1) and highlights genes mediating the diverse pharmacological responses to metformin treatment (Fig. 2). Knowledge of these pathways may help identify the genetic markers to predict variations in response as well as aid the tailoring of metformin therapy.