利拉鲁肽与 2 型糖尿病患者的肾脏结局。

Liraglutide and Renal Outcomes in Type 2 Diabetes.

机构信息

From KfH Kidney Center, Munich, and Friedrich Alexander University of Erlangen, Erlangen - both in Germany (J.F.E.M.); Novo Nordisk, Bagsvaerd, Denmark (D.D.Ø., K.B.-F., S.R., K.T.); University of Texas Southwestern Medical Center, Dallas (S.P.M.); Imperial College London, London (N.R.P.); Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto (B.Z.); and University of North Carolina School of Medicine, Chapel Hill (J.B.B.).

出版信息

N Engl J Med. 2017 Aug 31;377(9):839-848. doi: 10.1056/NEJMoa1616011.

DOI:10.1056/NEJMoa1616011

PMID:28854085

Abstract

BACKGROUND

In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown.

METHODS

We report the prespecified secondary renal outcomes of that randomized, controlled trial in which patients were assigned to receive liraglutide or placebo. The secondary renal outcome was a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease. The risk of renal outcomes was determined with the use of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rate and albuminuria were also analyzed.

RESULTS

A total of 9340 patients underwent randomization, and the median follow-up of the patients was 3.84 years. The renal outcome occurred in fewer participants in the liraglutide group than in the placebo group (268 of 4668 patients vs. 337 of 4672; hazard ratio, 0.78; 95% confidence interval [CI], 0.67 to 0.92; P=0.003). This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P=0.004). The rates of renal adverse events were similar in the liraglutide group and the placebo group (15.1 events and 16.5 events per 1000 patient-years), including the rate of acute kidney injury (7.1 and 6.2 events per 1000 patient-years, respectively).

CONCLUSIONS

This prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of diabetic kidney disease than placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .).

摘要

背景

在一项比较利拉鲁肽（一种胰高血糖素样肽 1 类似物）与安慰剂治疗伴有高心血管风险的 2 型糖尿病患者的随机对照试验中，我们发现利拉鲁肽可降低主要终点（非致死性心肌梗死、非致死性卒中和心血管原因导致的死亡）和死亡的风险。然而，利拉鲁肽对 2 型糖尿病患者肾脏结局的长期影响尚不清楚。

方法

我们报告了该随机对照试验的预先设定的次要肾脏结局，患者被随机分配接受利拉鲁肽或安慰剂治疗。次要肾脏结局是新发持续性大量白蛋白尿、血清肌酐水平持续倍增、终末期肾病或肾病导致的死亡的复合终点。采用意向治疗方法的时间事件分析来确定肾脏结局的风险。还分析了估算肾小球滤过率和白蛋白尿的变化。

结果

共有 9340 例患者接受了随机分组，患者的中位随访时间为 3.84 年。利拉鲁肽组的肾脏结局发生率低于安慰剂组（4668 例患者中 268 例 vs. 4672 例患者中 337 例；风险比，0.78；95%置信区间[CI]，0.67 至 0.92；P=0.003）。这一结果主要是由于新发持续性大量白蛋白尿的发生率降低，利拉鲁肽组的发生率低于安慰剂组（161 例 vs. 215 例；风险比，0.74；95%CI，0.60 至 0.91；P=0.004）。利拉鲁肽组和安慰剂组的肾脏不良事件发生率相似（每 1000 患者-年分别为 15.1 例和 16.5 例，包括急性肾损伤发生率[每 1000 患者-年分别为 7.1 例和 6.2 例]）。