Division of Cardiology, University of Texas Health Science Center, San Antonio, Texas.
Diabetes Obes Metab. 2020 Jan;22(1):16-29. doi: 10.1111/dom.13854. Epub 2019 Aug 30.
Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have been shown to mitigate the risks of cardiovascular (CV) and renal complications in patients with type 2 diabetes (T2D) and CV risk factors or CV disease (CVD). In CV outcomes trials (CVOTs) of patients with T2D and established CVD or multiple CV risk factors, empagliflozin and canagliflozin were associated with significant reductions in the risks of major adverse CV events (MACE), hospitalization for heart failure (HF) and kidney disease progression. In the DECLARE-TIMI 58 study, in which the majority of patients did not have established CVD, dapagliflozin was associated with significant reductions in the composite end point of CV death or hospitalization for HF and was noninferior to placebo with regard to MACE; although patients had relatively good renal function, dapagliflozin also showed renal benefits similar to those seen with empagliflozin and canagliflozin. This article reviews the increased risk of CVD and renal disease in patients with T2D and discusses the potential mechanisms of the cardioprotective and renoprotective effects of SGLT-2i therapy. The observed improvements in CV and renal outcomes with SGLT-2is in CVOTs suggest a class effect in this patient population and have influenced treatment guidelines for the way add-on therapy to metformin is initiated in patients with T2D and high CV risk. The overall cardioprotective and renoprotective effects of SGLT-2is in patients with T2D and high CV risk are most likely attributable to multiple mechanisms, including cardiac, haemodynamic, metabolic, anti-inflammatory and renal effects.
钠-葡萄糖共转运蛋白 2 抑制剂（SGLT-2i）已被证明可降低 2 型糖尿病（T2D）合并心血管（CV）危险因素或 CV 疾病（CVD）患者发生心血管（CV）和肾脏并发症的风险。在 T2D 合并已确诊 CVD 或存在多种 CV 危险因素患者的 CV 结局试验（CVOT）中，恩格列净和卡格列净可显著降低主要不良 CV 事件（MACE）、因心衰（HF）住院和肾脏疾病进展的风险。在DECLARE-TIMI 58 研究中，大多数患者没有确诊的 CVD，达格列净与 CV 死亡或 HF 住院复合终点的显著降低相关，且在 MACE 方面不劣于安慰剂；尽管患者的肾功能相对较好，达格列净也显示出与恩格列净和卡格列净相似的肾脏获益。本文综述了 T2D 患者 CVD 和肾脏疾病风险增加的情况，并讨论了 SGLT-2i 治疗的心脏保护和肾脏保护作用的潜在机制。CVOT 中 SGLT-2i 改善 CV 和肾脏结局的结果表明，在该患者人群中存在类效应，这影响了 T2D 患者和高 CV 风险患者起始二甲双胍附加治疗的治疗指南。SGLT-2i 在高 CV 风险的 T2D 患者中的整体心脏保护和肾脏保护作用可能归因于多种机制，包括心脏、血液动力学、代谢、抗炎和肾脏作用。
