2型糖尿病新一代降糖药的药物基因组学的最新进展

Recent advancesin pharmacogenetics of new-generation anti-diabetic medications for type 2 diabetes mellitus

精准医学是综合考虑个人的基因、环境和生活方式的一种新的疾病预防和治疗理念。随着药物遗传学和药物基因组学迅速发展和壮大,对个体遗传变异和药物剂量与治疗反应之间的联系进行研究,成为精准医学治疗的关键。2型糖尿病是一种以高血糖为特征的慢性代谢性疾病,可以导致心血管、肾脏等并发症。最新美国糖尿病协会和欧洲糖尿病协会的2型糖尿病高血糖管理共识中建议,合并动脉粥样硬化性心血管疾病(ASCVD)或慢性肾脏疾病、有低血糖风险或体质量相关问题的2型糖尿病患者,在二甲双胍单药起始治疗后优先使用胰高血糖素样肽-1(GLP-1)受体激动剂、钠-葡萄糖共转运体-2(SGLT2)抑制剂和二肽基肽酶-4(DPP-4)抑制剂。药物基因组学研究已经鉴定出许多与降糖药物反应相关的生物标志物,这些基因的功能变异对血糖控制、不良反应和并发症的风险有显著影响。我们综述了临床实践中新型二线降糖药物的药物遗传学的最新进展,为精准医学预防和治疗T2DM及其并发症提供有效工具。

Precision medicine is a scientific and medical practice for personalized therapy based upon individual genetic, environmental and lifestyle characteristics. Also pharmacogenetics and pharmacogenomics are rapidly developing and expanding as a key element of precision medicine. The association between individual genetic variabilities, drug disposition and therapeutic responses are examined. As a chronic metabolic disorder characterized by hyperglycemia, type 2 diabetes mellitus(T2 DM) leads to cardiovascular, renal and other complications. The latest consensus of American Diabetes Association and European Association for the Study of Diabetes(ADA-EASD) recommends preferential uses 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 diabetics with established atherosclerotic cardiovascular(ASCVD) or chronic kidney disease, risk of hypoglycemia or body weight-related problems. Several biomarkers associated with drug responses have been identified from 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. We summarized recent advances on pharmacogenetics of newer second-line anti-diabetic medications in clinical practices and discussed their therapeutic implications, offering useful tools for precision medicine in the treatment and prevention of T2 DM and its complications.