Fernandez-Fernandez Beatriz, Sarafidis Pantelis, Kanbay Mehmet, Navarro-González Juan F, Soler María José, Górriz Jose Luis, Ortiz Alberto
IIS-Fundacion Jimenez Diaz and School of Medicine, Universidad Autónoma de Madrid, Grupo Español de Estudio de la Nefropatia Diabetica, Madrid, Spain.
Spanish Renal Research Network, Madrid, Spain.
Clin Kidney J. 2020 Oct 9;13(5):728-733. doi: 10.1093/ckj/sfaa198. eCollection 2020 Oct.
Sodium-glucose co-transporter-2 (SGLT2) inhibitors decreased cardiovascular (CV) events and improved renal outcomes in CV safety studies in type 2 diabetes melitus (T2DM) patients at high CV risk. Canagliflozin also improved kidney outcomes in diabetic kidney disease in the Canagliflozin and Renal Events in Diabetes and Nephropathy Clinical Evaluationtrial. More recently, the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial showed that dapagliflozin improved CV outcomes in patients with HF with or without diabetes. Protection from HF in non-diabetics was confirmed for empagliflozin in the EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) trial. A meta-analysis of DAPA-HF and EMPEROR-Reduced confirmed reductions in all-cause and CV death and the combined risk of CV death or worsening HF, as well as in the composite renal endpoint {hazard ratio [HR] 0.62 [95% confidence interval (CI) 0.43-0.90]} without differences based on the presence of diabetes or baseline estimated glomerular filtration rate (eGFR). Moreover, the Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease (DAPA-CKD) showed that dapagliflozin as an add-on over renin-angiotensin system blockade in patients with chronic kidney disease (CKD; with or without T2DM) reduced the HR for the primary endpoint (time to the first occurrence of ≥50% eGFR decline, end-stage kidney disease or renal or CV death) to 0.61 (95% CI 0.51-0.72) and for the secondary endpoints of worsening renal function or death from kidney failure [HR 0.56 (95% CI 0.45-0.68)], hospitalization for HF or CV death [HR 0.71 (95% CI 0.55-0.92)] and all-cause mortality [HR 0.69 (95% CI 0.53-0.88)]. These beneficial effects were consistent in patients with and without T2DM. In conclusion, SGLT2 inhibitors offer CV and kidney protection in both diabetic and non-diabetic CKD and, additionally, improve glycaemic control in T2DM, making them first-line therapy for CKD independent from diabetic status.
在心血管高风险的2型糖尿病（T2DM）患者的心血管安全性研究中，钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂可降低心血管（CV）事件并改善肾脏预后。在卡格列净与糖尿病及肾病临床评估试验中的肾脏事件研究中，卡格列净也改善了糖尿病肾病患者的肾脏预后。最近，达格列净与心力衰竭不良结局预防（DAPA-HF）试验表明，达格列净可改善伴或不伴糖尿病的心力衰竭患者的CV结局。在射血分数降低的慢性心力衰竭患者的恩格列净结局试验（EMPEROR-Reduced）中，证实恩格列净可使非糖尿病患者免受心力衰竭影响。对DAPA-HF和EMPEROR-Reduced试验的荟萃分析证实，全因死亡和CV死亡以及CV死亡或心力衰竭恶化的综合风险均有所降低，在复合肾脏终点方面也是如此（风险比[HR] 0.62 [95%置信区间（CI）0.43 - 0.90]），且不受糖尿病或基线估计肾小球滤过率（eGFR）的影响。此外，评估达格列净对慢性肾脏病（CKD；伴或不伴T2DM）患者肾脏结局和心血管死亡率影响的研究（DAPA-CKD）表明，在CKD患者（伴或不伴T2DM）中，达格列净作为肾素 - 血管紧张素系统阻滞剂的附加治疗，将主要终点（首次出现≥50% eGFR下降、终末期肾病或肾脏或CV死亡的时间）的HR降至0.61（95% CI 0.51 - 0.72），将肾功能恶化或肾衰竭死亡的次要终点[HR 0.56（95% CI 0.45 - 0.68）]、因心力衰竭住院或CV死亡[HR 0.71（95% CI 0.55 - 0.92）]以及全因死亡率[HR 0.69（95% CI 0.53 - 0.88）]均降低。这些有益作用在伴或不伴T2DM的患者中均一致。总之，SGLT2抑制剂在糖尿病和非糖尿病CKD患者中均提供心血管和肾脏保护，此外，还可改善T2DM患者的血糖控制，使其成为独立于糖尿病状态的CKD一线治疗药物。
