Papakitsou Ioanna, Vougiouklakis George, Elisaf Moses S, Filippatos Theodosios D
Department of Internal Medicine, School of Medicine, University of Crete, University Hospital of Heraklion, Heraklion, Crete, Greece.
Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece.
Clin Pharmacol. 2019 Sep 19;11:133-143. doi: 10.2147/CPAA.S172353. eCollection 2019.
Dapagliflozin belongs in the family of sodium-glucose cotransporter 2 (SGLT2) inhibitors and acts by reducing glucose reabsorption in the proximal tubule. The aim of this review is to present the differential pharmacology and clinical utility of dapagliflozin. Dapagliflozin is orally administered, has a long half-life of 12.9 hours and (similar to empagliflozin) is a much weaker SGLT1 inhibitor compared with canagliflozin. Dapagliflozin significantly decreases glycated hemoglobin and fasting glucose levels in patients with type 2 diabetes mellitus (T2DM). The drug improves body weight, blood pressure, uric acid, triglycerides and high-density lipoprotein cholesterol. In the DECLARE-TIMI 58 trial, a large trial of 17,160 T2DM patients with established cardiovascular disease (CVD) or without established CVD but with multiple risk factors, dapagliflozin compared with placebo resulted in a significantly lower rate of the composite outcome of CVD death or hospitalization for heart failure (HHF); this effect was mainly due to a lower rate of HHF in the dapagliflozin group (HR: 0.73; 95%CI: 0.61-0.88), whereas no difference was observed in the rate of CVD death (HR: 0.98; 95%CI: 0.82-1.17). Moreover, dapagliflozin was noninferior to placebo with respect to major adverse CVD events. Dapagliflozin exerts beneficial effects on albuminuria. Additionally, in the DECLARE-TIMI 58 trial it significantly reduced the composite renal endpoint (40% decrease in glomerular filtration rate, end stage renal disease, or renal death) in both patients with established CVD and patients with multiple risk factors (overall HR: 0.53; 95%CI: 0.43-0.66). However dapagliflozin, like the other SGLT2 inhibitors, is associated with an increased risk of genital and urinary tract infections (usually mild mycotic infections) and acute kidney injury in cases of reduced extracellular volume. Dapagliflozin is a useful antidiabetic treatment which also exerts beneficial effects in the management of heart failure and diabetic kidney disease.
达格列净属于钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂家族，其作用机制是减少近端小管对葡萄糖的重吸收。本综述的目的是介绍达格列净的药理学差异和临床应用。达格列净口服给药，半衰期长达12.9小时，与恩格列净类似，与卡格列净相比，它是一种较弱的SGLT1抑制剂。达格列净可显著降低2型糖尿病（T2DM）患者的糖化血红蛋白和空腹血糖水平。该药可改善体重、血压、尿酸、甘油三酯和高密度脂蛋白胆固醇。在DECLARE-TIMI 58试验中，一项针对17160例患有已确诊心血管疾病（CVD）或无已确诊CVD但有多种危险因素的T2DM患者的大型试验中，与安慰剂相比，达格列净导致CVD死亡或因心力衰竭住院（HHF）的复合结局发生率显著降低；这种效果主要是由于达格列净组HHF发生率较低（HR：0.73；95%CI：0.61-0.88），而CVD死亡率未观察到差异（HR：0.98；95%CI：0.82-1.17）。此外，在主要不良CVD事件方面，达格列净不劣于安慰剂。达格列净对蛋白尿有有益作用。此外，在DECLARE-TIMI 58试验中，它在已确诊CVD的患者和有多种危险因素的患者中均显著降低了复合肾脏终点（肾小球滤过率降低40%、终末期肾病或肾脏死亡）（总体HR：0.53；95%CI：0.43-0.66）。然而，与其他SGLT2抑制剂一样，达格列净与生殖道和泌尿道感染（通常为轻度霉菌感染）风险增加以及细胞外液量减少时的急性肾损伤有关。达格列净是一种有用的抗糖尿病治疗药物，在心力衰竭和糖尿病肾病的管理中也发挥有益作用。
