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2型糖尿病的药物基因组学:口服抗糖尿病药物

Pharmacogenomics in type 2 diabetes: oral antidiabetic drugs.

作者信息

Daniels M A, Kan C, Willmes D M, Ismail K, Pistrosch F, Hopkins D, Mingrone G, Bornstein S R, Birkenfeld A L

机构信息

Department of Endocrinology, Diabetes and Nutrition, Charite-University School of Medicine, Berlin, Germany.

Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

出版信息

Pharmacogenomics J. 2016 Oct;16(5):399-410. doi: 10.1038/tpj.2016.54. Epub 2016 Jul 19.

Abstract

Type 2 diabetes mellitus (T2DM) is a fast progressing disease reaching pandemic proportions. T2DM is specifically harmful because of its severe secondary complications. In the course of the disease, most patients require treatment with oral antidiabetic drugs (OADs), for which a relatively large number of different options are available. The growing number of individuals affected by T2DM as well as marked interindividual differences in the response to treatment call for individualized therapeutic regimens that can maximize treatment efficacy and thus reduce side effects and costs. A large number of genetic polymorphisms have been described affecting the response to treatment with OADs; in this review, we summarize the most recent advances in this area of research. Extensive evidence exists for polymorphisms affecting pharmacokinetics and pharmacodynamics of biguanides and sulfonylureas. Data on incretin-based medications as well as the new class of sodium/glucose cotransporter 2 (SGLT2) inhibitors are just starting to emerge. With diabetes being a known comorbidity of several psychiatric disorders, we also review genetic polymorphisms possibly responsible for a common treatment response in both conditions. For all drug classes reviewed here, large prospective trials are necessary in order to consolidate the existing evidence and derive treatment schemes based on individual genetic traits.

摘要

2型糖尿病(T2DM)是一种迅速发展且已达到大流行程度的疾病。T2DM因其严重的继发性并发症而具有特殊的危害性。在疾病过程中,大多数患者需要使用口服抗糖尿病药物(OADs)进行治疗,目前有相对较多的不同选择。受T2DM影响的个体数量不断增加,以及对治疗反应存在显著的个体差异,这就需要个性化的治疗方案,以最大限度地提高治疗效果,从而减少副作用和成本。已经描述了大量影响OADs治疗反应的基因多态性;在本综述中,我们总结了该研究领域的最新进展。有大量证据表明基因多态性会影响双胍类药物和磺脲类药物的药代动力学和药效学。关于肠促胰岛素类药物以及新型钠/葡萄糖协同转运蛋白2(SGLT2)抑制剂的数据刚刚开始出现。由于糖尿病是几种精神疾病的已知合并症,我们还综述了可能导致这两种疾病出现共同治疗反应的基因多态性。对于本文所综述的所有药物类别,都需要进行大型前瞻性试验,以巩固现有证据并根据个体遗传特征制定治疗方案。

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