Scheen A J, Delanaye P
Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liège, Liège, Belgium; Clinical Pharmacology Unit, CHU Liège, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, Liège, Belgium.
Division of Nephrology, Dialysis, Transplantation and Hypertension, Department of Medicine, CHU Liège (ULg-CHU), Liège, Belgium.
Diabetes Metab. 2017 Apr;43(2):99-109. doi: 10.1016/j.diabet.2016.12.010. Epub 2017 Jan 30.
Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has enabled remarkable reductions in cardiovascular and all-cause mortality as well as in renal outcomes in patients with type 2 diabetes (T2D) and a history of cardiovascular disease in the EMPA-REG OUTCOME. These results have been attributed to haemodynamic rather than metabolic effects, in part due to the osmotic/diuretic action of empagliflozin and the reduction in arterial blood pressure (BP). The present narrative review includes the results of meta-analyses of trials evaluating the effects on renal outcomes of lowering BP in patients with T2D, with a special focus on the influence of baseline and achieved systolic BP, and compares the renal outcome results of the EMPA-REG OUTCOME with those of other major trials with inhibitors of the renin-angiotensin system in patients with T2D and the preliminary findings with other SGLT2 inhibitors, and also evaluates post hoc analyses from the EMPA-REG OUTCOME of special interest as regards the BP-lowering hypothesis and renal function. While systemic BP reduction associated to empagliflozin therapy may have contributed to the renal benefits reported in EMPA-REG OUTCOME, other local mechanisms related to kidney homoeostasis most probably also played a role in the overall protection observed in the trial.
恩格列净是一种钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂,在EMPA-REG OUTCOME研究中,已使2型糖尿病(T2D)合并心血管疾病史患者的心血管死亡率、全因死亡率以及肾脏结局显著降低。这些结果归因于血流动力学效应而非代谢效应,部分原因是恩格列净的渗透/利尿作用以及动脉血压(BP)降低。本叙述性综述纳入了评估降低T2D患者血压对肾脏结局影响的试验的荟萃分析结果,特别关注基线收缩压和达到的收缩压的影响,并将EMPA-REG OUTCOME研究的肾脏结局结果与其他针对T2D患者使用肾素-血管紧张素系统抑制剂的主要试验结果以及其他SGLT2抑制剂的初步研究结果进行比较,还评估了EMPA-REG OUTCOME研究中与降压假说和肾功能相关的特别感兴趣的事后分析。虽然恩格列净治疗导致的全身性血压降低可能对EMPA-REG OUTCOME研究中报告的肾脏益处有贡献,但与肾脏稳态相关的其他局部机制很可能也在该试验观察到的总体保护中发挥了作用。