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.

中文翻译：

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2型糖尿病患者的葡萄糖钠转运蛋白2转运蛋白抑制剂肾预后的改善：来自高或低肾脏风险患者的研究证据。

来自三项完整的心血管结局试验（CVOT），EMPA‐REG OUTCOME，CANVAS计划和DECLARE‐TIMI 58的数据补充了支持钠葡萄糖连接转运蛋白2（SGLT2）抑制剂对2型患者潜在的肾脏保护作用的证据。糖尿病。尽管最近的指南中提出了建议，但很难支持这样的观点，即从这些SGLT2抑制剂CVOT结果中获得了肾脏保护的确凿证据。迄今为止，唯一可报告有关SGLT2抑制肾影响的确切数据的专门试验是CREDENCE。值得注意的是，在CREDENCE中观察到的与患者相关的肾脏终点事件（透析，移植或肾死亡）的总数显着高于所有三个CVOT的总数（分别为183事件/ 4401患者vs. 69事件/ 34 322患者） ），这显示了CREDENCE对这些肾脏终点的统计功能增强。Canagliflozin的治疗可将晚期肾脏疾病的主要复合终点的相对危险度降低（RRR）30％，血清肌酐增加一倍或因肾脏或心血管原因死亡，并且针对肾特异性元素的RRR降低34％该主要终点（P <0.001）。因此，除了2型糖尿病的血糖控制和降低心血管风险外，Canagliflozin已成为首个获得美国批准的SGLT2抑制剂，其中包括RRR适应症。在证实CVOT的探索性数据的同时，CREDENCE提供了首个关于卡格列净对患者相关肾脏终点影响的可靠数据。除非有其他SGLT2抑制剂的其他肾脏试验被报道，否则不能推断SGLT2抑制剂类作用的结论。