Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Postgrad Med. 2019 Aug;131(6):367-375. doi: 10.1080/00325481.2019.1624582. Epub 2019 Jun 5.
In patients with type 2 diabetes (T2D), microvascular changes in the kidney often result in diabetic kidney disease (DKD), the progression of which is associated with an increased risk of cardiovascular (CV) and all-cause mortality. Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are a newer class of oral glucose-lowering therapies that were associated with significant reductions in the risk of major adverse CV events, CV death, and hospitalization for heart failure compared with placebo in CV outcomes trials (CVOTs) of patients with T2D and established CV disease or varying levels of CV risk. In addition, SGLT-2is reduced the risks of clinically relevant renal outcomes in these large randomized studies, indicating the potential for renoprotective effects in patients with T2D and DKD. This review discussed the non-glycemic effects of SGLT-2is in patients with T2D and renal impairment, including reductions in systolic and diastolic blood pressure, decreases in albuminuria and plasma uric acid, changes in estimated glomerular filtration rate, and minimal changes in electrolytes. Potential mechanisms for the renoprotective effects of SGLT-2is observed in CVOTs were considered, including the likely incremental benefits of SGLT-2is when added to renin-aldosterone-angiotensin system inhibitors (RAASis). The possibility of extending the use of SGLT-2is to patients with non-DKD was also discussed. Although the exact mechanisms by which SGLT-2is improve renal outcomes are not fully understood, they are likely to be multifactorial and additive when these drugs are used in combination with RAASis in patients with DKD.
在 2 型糖尿病（T2D）患者中，肾脏的微血管变化通常会导致糖尿病肾病（DKD），其进展与心血管（CV）和全因死亡率的风险增加相关。钠-葡萄糖共转运蛋白 2 抑制剂（SGLT-2is）是一类新型的口服降糖药物，与安慰剂相比，在 T2D 患者和已确诊的 CV 疾病或不同程度的 CV 风险的 CV 结局试验（CVOT）中，SGLT-2is 显著降低了主要不良 CV 事件、CV 死亡和心力衰竭住院的风险。此外，在这些大型随机研究中，SGLT-2is 降低了临床相关肾脏结局的风险，表明 SGLT-2is 在 T2D 和 DKD 患者中具有潜在的肾脏保护作用。本文讨论了 SGLT-2is 在 T2D 合并肾功能不全患者中的非血糖作用，包括收缩压和舒张压降低、白蛋白尿和血浆尿酸降低、估算肾小球滤过率变化以及电解质变化最小。还考虑了 SGLT-2is 在 CVOT 中观察到的肾脏保护作用的潜在机制，包括 SGLT-2is 与肾素-血管紧张素-醛固酮系统抑制剂（RAASis）联合使用时可能会增加获益。还讨论了将 SGLT-2is 扩展用于非 DKD 患者的可能性。尽管 SGLT-2is 改善肾脏结局的确切机制尚未完全阐明，但在 DKD 患者中与 RAASis 联合使用时，它们可能是多因素的和累加的。
