恩格列净与 2 型糖尿病患者的肾脏疾病进展。
Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes.
机构信息
From the Department of Medicine, Division of Nephrology, Würzburg University Clinic, Würzburg (C.W.), and Boehringer Ingelheim Pharma, Ingelheim (M.E., M.M., H.J.W., U.C.B.) - both in Germany; the Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.); the Biostatistics Center, George Washington University, Rockville, MD (J.M.L.); the Divisions of Cardiology (D.F.) and Endocrinology (B.Z.), University of Toronto, and the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (B.Z.) - both in Toronto; and Boehringer Ingelheim Norway, Asker, Norway (O.E.J.).
出版信息
N Engl J Med. 2016 Jul 28;375(4):323-34. doi: 10.1056/NEJMoa1515920. Epub 2016 Jun 14.
BACKGROUND
Diabetes confers an increased risk of adverse cardiovascular and renal events. In the EMPA-REG OUTCOME trial, empagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes at high risk for cardiovascular events. We wanted to determine the long-term renal effects of empagliflozin, an analysis that was a prespecified component of the secondary microvascular outcome of that trial.
METHODS
We randomly assigned patients with type 2 diabetes and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m(2) of body-surface area to receive either empagliflozin (at a dose of 10 mg or 25 mg) or placebo once daily. Prespecified renal outcomes included incident or worsening nephropathy (progression to macroalbuminuria, doubling of the serum creatinine level, initiation of renal-replacement therapy, or death from renal disease) and incident albuminuria.
RESULTS
Incident or worsening nephropathy occurred in 525 of 4124 patients (12.7%) in the empagliflozin group and in 388 of 2061 (18.8%) in the placebo group (hazard ratio in the empagliflozin group, 0.61; 95% confidence interval, 0.53 to 0.70; P<0.001). Doubling of the serum creatinine level occurred in 70 of 4645 patients (1.5%) in the empagliflozin group and in 60 of 2323 (2.6%) in the placebo group, a significant relative risk reduction of 44%. Renal-replacement therapy was initiated in 13 of 4687 patients (0.3%) in the empagliflozin group and in 14 of 2333 patients (0.6%) in the placebo group, representing a 55% lower relative risk in the empagliflozin group. There was no significant between-group difference in the rate of incident albuminuria. The adverse-event profile of empagliflozin in patients with impaired kidney function at baseline was similar to that reported in the overall trial population.
CONCLUSIONS
In patients with type 2 diabetes at high cardiovascular risk, empagliflozin was associated with slower progression of kidney disease and lower rates of clinically relevant renal events than was placebo when added to standard care. (Funded by the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance; EMPA-REG OUTCOME ClinicalTrials.gov number, NCT01131676.).
背景
糖尿病会增加心血管和肾脏不良事件的风险。在 EMPA-REG OUTCOME 试验中，钠-葡萄糖协同转运蛋白 2 抑制剂恩格列净降低了心血管事件高危 2 型糖尿病患者的主要不良心血管事件风险。我们想要确定恩格列净的长期肾脏效果，这是该试验次要微血管终点的预先指定分析部分。
方法
我们将肾小球滤过率（eGFR）至少为 30 ml/min/1.73 m² 的 2 型糖尿病患者随机分为恩格列净（剂量为 10 mg 或 25 mg）或安慰剂组，每日一次。预先指定的肾脏结局包括新发或恶化的肾病（进展为大量白蛋白尿、血清肌酐水平翻倍、开始肾脏替代治疗或因肾脏疾病死亡）和新发蛋白尿。
结果
恩格列净组 4124 例患者中有 525 例（12.7%）发生新发或恶化的肾病，安慰剂组 2061 例患者中有 388 例（18.8%）（恩格列净组的危险比为 0.61；95%置信区间为 0.53 至 0.70；P<0.001）。恩格列净组 4645 例患者中有 70 例（1.5%）血清肌酐水平翻倍，安慰剂组 2323 例患者中有 60 例（2.6%），相对风险降低 44%。恩格列净组 4687 例患者中有 13 例（0.3%）开始肾脏替代治疗，安慰剂组 2333 例患者中有 14 例（0.6%），恩格列净组相对风险降低 55%。两组间新发蛋白尿发生率无显著差异。在基线肾功能受损的患者中，恩格列净的不良事件谱与总体试验人群报告的相似。
结论
在心血管风险较高的 2 型糖尿病患者中，与安慰剂相比，恩格列净与标准治疗联合使用可减缓肾脏疾病的进展，并降低有临床意义的肾脏事件发生率。（由勃林格殷格翰和礼来公司糖尿病联盟资助；EMPA-REG OUTCOME 临床试验.gov 编号，NCT01131676。）
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