Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, 151401, India.
Department of Radiology, AIIMS, Bathinda, 151001, India.
Eur J Pharmacol. 2022 Dec 5;936:175356. doi: 10.1016/j.ejphar.2022.175356. Epub 2022 Oct 28.
Type 2 Diabetes mellitus (T2DM) is a multifactorial metabolic disorder also known as a silent killer disease. Macrovascular and microvascular complications associated with diabetes worsen the condition leading to higher comorbidity and mortality rate. Currently, available treatment strategies for diabetes include biguanides, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, insulin and its analogs, DPP-4 (dipeptidyl-peptidase-4) inhibitors, SGLT-2 inhibitors, and Glucagon Like Peptide-1 receptor agonists (GLP-1RAs). Synthetic agonists of GLP-1 hormone, GLP-1RAs are an emerging class of anti-diabetic drugs which target the pathophysiology of diabetes through various mechanisms and at multiple sites. They promote insulin secretion from beta cells, and the proliferation of beta cells inhibits glucagon secretion, delays gastric emptying and induces satiety. However, treatment is reported to be associated with inter-individual variations and adverse drug reactions, which are also influenced by genetic variations. There have been a few pharmacogenetic studies have been carried out on this drug class. This review discusses all the available GLP-1RAs, their pharmacokinetics, pharmacodynamics and genetic variation affecting the inter-individual variation.
2 型糖尿病（T2DM）是一种多因素代谢紊乱疾病，也被称为无声杀手疾病。与糖尿病相关的大血管和微血管并发症会使病情恶化，导致更高的合并症和死亡率。目前，糖尿病的可用治疗策略包括双胍类、磺酰脲类、α-葡萄糖苷酶抑制剂、噻唑烷二酮类、胰岛素及其类似物、DPP-4（二肽基肽酶-4）抑制剂、SGLT-2 抑制剂和胰高血糖素样肽-1 受体激动剂（GLP-1RAs）。GLP-1 激素的合成激动剂，GLP-1RAs 是一类新兴的抗糖尿病药物，通过多种机制和多个靶点针对糖尿病的病理生理学。它们促进β细胞分泌胰岛素，并抑制胰高血糖素分泌、延缓胃排空和诱导饱腹感。然而，据报道，这种治疗方法与个体间的差异和药物不良反应有关，这些差异也受到遗传变异的影响。已经对这种药物类别进行了一些药物遗传学研究。本综述讨论了所有可用的 GLP-1RAs 及其药代动力学、药效学以及影响个体间差异的遗传变异。
