Chitkara College of Pharmacy, Chitkara University, Punjab, India.
Curr Mol Pharmacol. 2021 Oct 25;14(4):487-497. doi: 10.2174/1874467213666201012161439.
A chronic metabolic disease, diabetes mellitus (DM), is associated with various comorbidities that considerably decrease the quality of life. Sodium glucose linked transporter 2 (SGLT2) receptors are mainly situated in the proximal tubule of nephron. About 90% of glucose concentration is reabsorbed by these receptors in the nephron. The advanced remedy for the management of DM is sodium glucose co-transporter 2 inhibitors (SGLT2-Is), which inhibits or lowers the reabsorption of glucose. Furthermore, SGLT2-Is enhance the elimination of glucose level in urine (glycosuria). Empagliglozin, canagliflozin, ertugliflozin and dapagliflozin are the standard medications which have been authorized recently, for the management of DM by The Food and Drug Administration (FDA). Besides, having optimistic efficacy to attenuate blood glucose level, these medications have exhibited impressive cardioprotective and renoprotective effects in major clinical trials. Unlike other hypoglycaemic medications, it is found that these agents help in a consistent reduction in hospitalization, due to heart failure with probably multifactorial mechanisms. The cardioprotective efficacy of SGLT2-Is is characterized by enhancement in ventricular loading condition, in metabolism of cardiac cell, adipokines alteration, cardiac fibrosis, and reduction in the necrosis of cardiac cell. Recently confirmed results depict that dapagliflozin gradually decreases the frequency of co-morbidity and mortality in heart failure patients. The present review explores the mechanistic principle and the clinical trial data of SGLT2-Is, which further support cardioprotective effects associated with these medications.
一种慢性代谢疾病,糖尿病(DM),与各种合并症有关,这些合并症大大降低了生活质量。钠-葡萄糖共转运蛋白 2(SGLT2)受体主要位于近曲小管的肾单位。大约 90%的葡萄糖浓度通过这些受体在肾单位中被重吸收。DM 管理的先进治疗方法是钠-葡萄糖协同转运蛋白 2 抑制剂(SGLT2-Is),它可以抑制或降低葡萄糖的重吸收。此外,SGLT2-Is 可增强尿中葡萄糖水平的排泄(糖尿)。恩格列净、卡格列净、依帕列净和达格列净是最近被美国食品和药物管理局(FDA)批准用于 DM 管理的标准药物。此外,这些药物除了具有降低血糖水平的积极疗效外,在主要临床试验中还表现出了令人印象深刻的心脏和肾脏保护作用。与其他降血糖药物不同,研究发现这些药物有助于一致减少因心力衰竭而住院的次数,这可能与多种机制有关。SGLT2-Is 的心脏保护作用的特点是增强心室负荷条件、心脏细胞代谢、脂联素改变、心脏纤维化和减少心脏细胞坏死。最近证实的结果表明,达格列净可逐渐降低心力衰竭患者的合并症和死亡率。本综述探讨了 SGLT2-Is 的作用机制和临床试验数据,进一步支持了这些药物的心脏保护作用。