Heo Chan Uk, Choi Chang-Ik
College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Korea.
J Clin Med. 2019 Mar 21;8(3):393. doi: 10.3390/jcm8030393.
Precision medicine is a scientific and medical practice for personalized therapy based on patients' individual genetic, environmental, and lifestyle characteristics. Pharmacogenetics and pharmacogenomics are also rapidly developing and expanding as a key element of precision medicine, in which the association between individual genetic variabilities and drug disposition and therapeutic responses are investigated. Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia mainly associated with insulin resistance, with the risk of clinically important cardiovascular, neurological, and renal complications. The latest consensus report from the American Diabetes Association and European Association for the Study of Diabetes (ADA-EASD) on the management of T2D recommends preferential use of glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and some dipeptidyl peptidase-4 (DPP-4) inhibitors after initial metformin monotherapy for diabetic patients with established atherosclerotic cardiovascular or chronic kidney disease, and with risk of hypoglycemia or body weight-related problems. In this review article, we summarized current progress on pharmacogenetics of newer second-line antidiabetic medications in clinical practices and discussed their therapeutic implications for precision medicine in T2D management. Several biomarkers associated with drug responses have been identified from extensive clinical pharmacogenetic studies, and functional variations in these genes have been shown to significantly affect drug-related glycemic control, adverse reactions, and risk of diabetic complications. More comprehensive pharmacogenetic research in various clinical settings will clarify the therapeutic implications of these genes, which may be useful tools for precision medicine in the treatment and prevention of T2D and its complications.
精准医学是一种基于患者个体的基因、环境和生活方式特征进行个性化治疗的科学和医学实践。药物遗传学和药物基因组学作为精准医学的关键要素也在迅速发展和扩展，其中研究了个体基因变异与药物处置及治疗反应之间的关联。2型糖尿病（T2D）是一种慢性代谢紊乱疾病，其特征为高血糖，主要与胰岛素抵抗相关，存在临床上重要的心血管、神经和肾脏并发症风险。美国糖尿病协会和欧洲糖尿病研究协会（ADA - EASD）关于T2D管理的最新共识报告建议，对于已确诊患有动脉粥样硬化性心血管疾病或慢性肾病、有低血糖风险或体重相关问题的糖尿病患者，在初始使用二甲双胍单药治疗后，优先使用胰高血糖素样肽 - 1（GLP - 1）受体激动剂、钠 - 葡萄糖协同转运蛋白 - 2（SGLT2）抑制剂和一些二肽基肽酶 - 4（DPP - 4）抑制剂。在这篇综述文章中，我们总结了临床实践中新型二线抗糖尿病药物的药物遗传学研究现状，并讨论了它们在T2D管理中对精准医学的治疗意义。通过广泛的临床药物遗传学研究已经确定了几种与药物反应相关的生物标志物，并且这些基因的功能变异已被证明会显著影响与药物相关的血糖控制、不良反应以及糖尿病并发症风险。在各种临床环境中进行更全面的药物遗传学研究将阐明这些基因的治疗意义，它们可能是治疗和预防T2D及其并发症的精准医学的有用工具。
