From the Department Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands (H.J.L.H.); the George Institute for Global Health, Sydney (H.J.L.H., D.C.W.); Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden (B.V.S., M.L., C.D.S., A.-M.L.); the National Medical Science and Nutrition Institute Salvador Zubirán, Mexico City (R.C.-R.); the Departments of Medicine and Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA (G.M.C.); the Study Design and Biostatistics Center, University of Utah Health Sciences, Salt Lake City (T.G.); the Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, Guangzhou, China (F.-F.H.); KfH Kidney Center, Munich, and Department of Medicine 4, University of Erlangen-Nuremberg, Erlangen - both in Germany (J.F.E.M.); the Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow (J.J.V.M.), and the Department of Renal Medicine, University College London, London (D.C.W.) - both in the United Kingdom; Steno Diabetes Center Copenhagen, Gentofte, and the Department of Clinical Medicine, University of Copenhagen, Copenhagen - both in Denmark (P.R.); and the Department of Internal Medicine, UT Southwestern Medical Center, Dallas (R.D.T.).
N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24.
Patients with chronic kidney disease have a high risk of adverse kidney and cardiovascular outcomes. The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known.
We randomly assigned 4304 participants with an estimated glomerular filtration rate (GFR) of 25 to 75 ml per minute per 1.73 m of body-surface area and a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 200 to 5000 to receive dapagliflozin (10 mg once daily) or placebo. The primary outcome was a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes.
The independent data monitoring committee recommended stopping the trial because of efficacy. Over a median of 2.4 years, a primary outcome event occurred in 197 of 2152 participants (9.2%) in the dapagliflozin group and 312 of 2152 participants (14.5%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.51 to 0.72; P<0.001; number needed to treat to prevent one primary outcome event, 19 [95% CI, 15 to 27]). The hazard ratio for the composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal causes was 0.56 (95% CI, 0.45 to 0.68; P<0.001), and the hazard ratio for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI, 0.55 to 0.92; P = 0.009). Death occurred in 101 participants (4.7%) in the dapagliflozin group and 146 participants (6.8%) in the placebo group (hazard ratio, 0.69; 95% CI, 0.53 to 0.88; P = 0.004). The effects of dapagliflozin were similar in participants with type 2 diabetes and in those without type 2 diabetes. The known safety profile of dapagliflozin was confirmed.
Among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo. (Funded by AstraZeneca; DAPA-CKD ClinicalTrials.gov number, NCT03036150.).
患有慢性肾病的患者发生不良肾脏和心血管结局的风险较高。对于患有慢性肾病且伴有或不伴有 2 型糖尿病的患者，达格列净的疗效尚不明确。
我们将 4304 名肾小球滤过率（GFR）估计值为 25 至 75ml/分钟/1.73m2 且尿白蛋白与肌酐比值（以毫克计白蛋白和以克计肌酐）为 200 至 5000 的患者随机分配至接受达格列净（每日 10mg）或安慰剂治疗。主要复合终点为估计 GFR 持续下降至少 50%、终末期肾病或因肾脏或心血管原因死亡。
独立数据监测委员会因疗效建议停止试验。中位随访时间为 2.4 年，达格列净组有 197 例（9.2%）患者和安慰剂组有 312 例（14.5%）患者发生主要终点事件（风险比，0.61；95%置信区间[CI]，0.51 至 0.72；P<0.001；预防 1 例主要终点事件需要治疗的患者数，19[95%CI，15 至 27]）。估计 GFR 持续下降至少 50%、终末期肾病或因肾脏原因死亡的复合终点的风险比为 0.56（95%CI，0.45 至 0.68；P<0.001），因心血管原因死亡或因心力衰竭住院的复合终点的风险比为 0.71（95%CI，0.55 至 0.92；P=0.009）。达格列净组有 101 例（4.7%）患者和安慰剂组有 146 例（6.8%）患者死亡（风险比，0.69；95%CI，0.53 至 0.88；P=0.004）。在患有 2 型糖尿病和不患有 2 型糖尿病的患者中，达格列净的作用相似。达格列净已知的安全性特征得到了证实。
在患有慢性肾病的患者中，无论是否患有糖尿病，与安慰剂相比，达格列净可显著降低估计 GFR 持续下降至少 50%、终末期肾病或因肾脏或心血管原因死亡的复合终点风险。（由阿斯利康公司资助；DAPA-CKD ClinicalTrials.gov 编号，NCT03036150。）
