Department of Medicine I, Rudolfstitung Hospital, Vienna, Austria.
Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Diabetes Obes Metab. 2020 Jul;22(7):1024-1034. doi: 10.1111/dom.13994. Epub 2020 Mar 2.
Data from three completed cardiovascular outcome trials (CVOTs), EMPA-REG OUTCOME, CANVAS Program and DECLARE-TIMI 58, add to the evidence supporting the potential renoprotective effects of sodium-glucose linked transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes. Despite recommendations in recent guidelines, it is difficult to support a view that definitive evidence for renoprotection exists from these SGLT2 inhibitor CVOT results. To date, the only dedicated trial to report definitive data on the renal impact of SGLT2 inhibition is CREDENCE. Notably, the total number of patient-relevant renal endpoint events (dialysis, transplant or renal death) observed in CREDENCE was significantly higher than the total for all three CVOTs collectively (183 events/4401 patients vs. 69 events/34 322 patients, respectively), which shows the increased statistical power of CREDENCE for these renal endpoints. Treatment with canagliflozin was associated with a 30% relative risk reduction (RRR) in the primary composite endpoint of end-stage kidney disease, doubling of serum creatinine, or death from renal or cardiovascular causes and a 34% RRR for the renal-specific elements of this primary endpoint (P <0.001). Canagliflozin has therefore become the first US-approved SGLT2 inhibitor to include an indication for RRR, in addition to type 2 diabetes glycaemic control and cardiovascular risk reduction. While confirmatory of the exploratory data from CVOTs, CREDENCE provides the first robust data on the effects of canagliflozin on patient-relevant renal endpoints. Extrapolation to a conclusion of a SGLT2 inhibitor class effect cannot be made until additional renal trials with other SGLT2 inhibitors are reported.
来自三项已完成的心血管结局试验（CVOT）——恩格列净心血管结局研究（EMPA-REG OUTCOME）、卡格列净心血管评估研究（CANVAS Program）和 DECLARE-TIMI 58 的数据进一步支持了钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂在 2 型糖尿病患者中的潜在肾脏保护作用。尽管最近的指南中有相关推荐，但从这些 SGLT2 抑制剂 CVOT 结果中得出明确的肾脏保护证据仍然难以令人信服。迄今为止，唯一一项专门报告 SGLT2 抑制对肾脏影响的确定性数据的试验是 CREDENCE。值得注意的是，CREDENCE 观察到的与患者相关的肾脏终点事件（透析、移植或肾脏死亡）总数明显高于三项 CVOT 的总和（183 例/4401 例患者与 69 例/34322 例患者，分别），这表明 CREDENCE 对这些肾脏终点事件具有更高的统计学效能。卡格列净治疗与主要复合终点（终末期肾病、血清肌酐加倍或因肾脏或心血管原因死亡）的风险比降低 30%（RRR）相关，该主要终点的肾脏特异性元素的 RRR 为 34%（P<0.001）。因此，卡格列净成为第一个获得美国批准的 SGLT2 抑制剂，除了用于 2 型糖尿病血糖控制和降低心血管风险外，还可用于降低风险获益比。虽然证实了 CVOT 的探索性数据，但 CREDENCE 提供了关于卡格列净对患者相关肾脏终点影响的首个稳健数据。在报告其他 SGLT2 抑制剂的肾脏试验之前，不能对 SGLT2 抑制剂类药物的作用得出结论。
