In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized, placebo-controlled trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin significantly reduced risk of kidney failure and prolonged survival in patients with CKD with or without type 2 diabetes.

Adults with eGFR of 25–75 ml/min per 1.73 m² and urinary albumin-to-creatinine ratio of 200–5000 mg/g had been randomized to receive dapagliflozin 10 mg/d or placebo. Here, we conducted a prespecified analysis of dapagliflozin’s effects in patients with stage 4 CKD (eGFR,30 ml/min per 1.73 m²) at baseline. The primary end point was a composite of time to ≥50% sustained decline in eGFR, ESKD, or kidney or cardiovascular death. Secondary end points were a kidney composite (same as the primary end point but without cardiovascular death), a composite of cardiovascular death or heart failure hospitalization, and all-cause death.

A total of 293 participants with stage 4 CKD received dapagliflozin and 331 received placebo. Patients with stage 4 CKD randomized to dapagliflozin experienced a 27% (95% confidence interval [95% CI]: –2 to 47%) reduction in the primary composite endpoint, and 29% (–2 to 51%), 17% (–53 to 55%), and 32% (–21 to 61%) reductions in the kidney, cardiovascular and mortality endpoints, respectively, relative to placebo. Interaction P-values were 0.22, 0.13, 0.63, and 0.95, respectively, comparing CKD stages 4 versus 2/3. The eGFR slope declined by 2.15 and 3.38 ml/min per 1.73 m² per year in the dapagliflozin and placebo groups, respectively (P=0.005). Patients treated with dapagliflozin or placebo had similar rates of serious adverse events and adverse events of interest.

Among patients with stage 4 CKD and albuminuria, the effects of dapagliflozin were consistent with those observed in the DAPA-CKD trial overall, with no evidence of increased risks.

在达格列净和慢性肾脏病不良后果预防 (DAPA-CKD) 随机、安慰剂对照试验中，钠-葡萄糖协同转运蛋白 2 抑制剂达格列净显着降低伴或不伴 2 型 CKD 患者的肾衰竭风险并延长生存期糖尿病。

eGFR 为 25-75 ml/min/1.73 m ²且尿白蛋白与肌酐比为 200-5000 mg/g 的成人被随机分配接受达格列净 10 mg/d 或安慰剂。在这里，我们对达格列净在基线时对 4 期 CKD 患者（eGFR，30 毫升/分钟每 1.73 m ^{2 ）的影响进行了预先指定的分析。}主要终点是 eGFR 持续下降 ≥ 50%、ESKD 或肾脏或心血管死亡的复合终点。次要终点是肾脏复合终点（与主要终点相同，但没有心血管死亡）、心血管死亡或心力衰竭住院和全因死亡的复合终点。

共有 293 名患有 4 期 CKD 的参与者接受了达格列净，331 名参与者接受了安慰剂。随机分配至达格列净的 4 期 CKD 患者的主要复合终点降低了 27%（95% 置信区间 [95% CI]：–2 至 47%），以及 29%（–2 至 51%）、17%（与安慰剂相比，肾脏、心血管和死亡率终点分别降低 –53% 至 55%）和 32%（–21% 至 61%）。交互 P 值分别为 0.22、0.13、0.63 和 0.95，比较 CKD 阶段 4 和 2/3。达格列净组和安慰剂组的 eGFR 斜率分别下降了 2.15 和 3.38 ml/min/1.73 m ^{2 (} P =0.005)。接受达格列净或安慰剂治疗的患者发生严重不良事件和感兴趣的不良事件的发生率相似。

在患有 4 期 CKD 和白蛋白尿的患者中，达格列净的效果与 DAPA-CKD 试验中观察到的整体效果一致，没有增加风险的证据。