Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, 151401, India.
Eur J Pharmacol. 2021 Aug 5;904:174169. doi: 10.1016/j.ejphar.2021.174169. Epub 2021 May 11.
Diabetes, characterized by high glucose levels, has been listed to be one of the world's major causes of death. Around 1.6 million deaths are attributed to this disease each year. Persistent hyperglycemic conditions in diabetic patients affect various organs of the body leading to diabetic complications and worsen the disease condition. Current treatment strategies for diabetes include biguanides, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, insulin and its analogs, DPP-4(dipeptidyl peptidase-4) and GLP-1 (glucagon-like peptide) analogs. However, many side effects contributing to the devastation of the disease are associated with them. Sodium glucose co-transporter-2 (SGLT2) inhibition has been reported to be new insulin-independent approach to diabetes therapy. It blocks glucose uptake in the kidneys by inhibiting SGLT2 transporters, thereby promoting glycosuria. Dapagliflozin, empagliflozin and canagliflozin are the most widely used SGLT2 inhibitors. They are effective in controlling blood glucose and HbA1c levels with few side effects including hypoglycemia or weight gain which makes them preferable to other anti-diabetic drugs. However, treatment is found to be associated with inter-individual drug response to SGLT2 inhibitors and adverse drug reactions which are also affected by genetic variations. There have been very few pharmacogenetics trials of these drugs. This review discusses the various SGLT2 inhibitors, their pharmacokinetics, pharmacodynamics and genetic variation influencing the inter-individual drug response.
糖尿病的特征是血糖水平升高，已被列为世界上主要的死亡原因之一。每年约有 160 万人因此病死亡。糖尿病患者持续的高血糖状况会影响身体的各个器官，导致糖尿病并发症，并使病情恶化。目前糖尿病的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）和 GLP-1（胰高血糖素样肽）类似物。然而，许多导致疾病恶化的副作用与之相关。钠-葡萄糖协同转运蛋白 2（SGLT2）抑制已被报道为一种新的非胰岛素依赖的糖尿病治疗方法。它通过抑制 SGLT2 转运蛋白来阻止肾脏对葡萄糖的摄取，从而促进糖尿。达格列净、恩格列净和卡格列净是最广泛使用的 SGLT2 抑制剂。它们在控制血糖和 HbA1c 水平方面非常有效，且副作用较少，包括低血糖或体重增加，这使它们优于其他抗糖尿病药物。然而，治疗被发现与 SGLT2 抑制剂的个体间药物反应和不良反应有关，这些不良反应也受到遗传变异的影响。这些药物的药物遗传学试验非常少。本文讨论了各种 SGLT2 抑制剂及其药代动力学、药效学和遗传变异对个体间药物反应的影响。
