Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy.
Division of Nephrology, Department of Advanced Medical and Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy.
Diabetes Obes Metab. 2019 Aug;21(8):1790-1800. doi: 10.1111/dom.13743. Epub 2019 May 2.
Diabetic kidney disease (DKD) still remains a progressive condition that is associated with higher risk of end-stage kidney disease and significant cardiovascular morbidity and mortality. Twelve cardiovascular outcome trials in type 2 diabetes (T2D) have been published to date. Most trials with dipeptidyl-peptidase inhibitors (SAVOR-TIMI 53 with saxagliptin, EXAMINE with alogliptin, TECOS with sitagliptin, and CARMELINA with linagliptin) and with glucagon-like peptide-1 receptor agonists (GLP-1RAs) (ELIXA with lixisenatide, LEADER with liraglutide, SUSTAIN-6 with semaglutide, EXCSEL with exenatide once-weekly, and HARMONY with albiglutide) pointed towards reduced albuminuria, which is a surrogate endpoint possibly heralding renal function preservation. The three trials with sodium-glucose co-transporter-2 inhibitors (SGLT-2is) (empagliflozin, canagliflozin and dapagliflozin) also showed a salutary effect on long-term estimated glomerular filtration rate, suggesting that SGLT-2is are more effective at mitigating loss of kidney function than incretin-based therapies; moreover, SGLT-2is also have the advantage of plausible haemodynamic mechanisms for improved renal outcomes. Despite some residual limitations linked to differences in study populations and patient characteristics, the cardiorenal protective actions of SGLT-2is, and to a lesser extent some GLP-1RAs, make them favourable medications for patients with T2D at increased cardiorenal risk. There is room for optimism that their use may change the paradigm of the ineluctable progression of DKD.
糖尿病肾病（DKD）仍然是一种进行性疾病，与终末期肾病风险增加以及重大心血管发病率和死亡率显著相关。迄今为止，已经发表了 12 项针对 2 型糖尿病（T2D）的心血管结局试验。大多数二肽基肽酶抑制剂（SAVOR-TIMI 53 与沙格列汀、EXAMINE 与阿格列汀、TECOS 与西格列汀和 CARMELINA 与利格列汀）和胰高血糖素样肽-1 受体激动剂（GLP-1RAs）（ELIXA 与利西那肽、LEADER 与利拉鲁肽、SUSTAIN-6 与司美格鲁肽、EXCSEL 与每周一次的艾塞那肽和 HARMONY 与阿必鲁肽）的试验都指向减少白蛋白尿，这是一个可能预示肾功能保护的替代终点。三种钠-葡萄糖共转运蛋白-2 抑制剂（SGLT-2is）（恩格列净、卡格列净和达格列净）的试验也显示对长期估计肾小球滤过率有有益的影响，表明 SGLT-2is 在减轻肾功能丧失方面比基于肠促胰岛素的治疗更有效；此外，SGLT-2is 还有可能通过改善肾脏结局的血流动力学机制发挥作用。尽管由于研究人群和患者特征的差异存在一些残余局限性，但 SGLT-2is 的心脏肾脏保护作用，以及在较小程度上的一些 GLP-1RAs，使它们成为心血管肾风险增加的 T2D 患者的有利药物。乐观的是，它们的使用可能会改变 DKD 不可避免进展的模式。
