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利拉鲁肽对2型糖尿病肾脏结局的影响研究
Liraglutide and Renal Outcomes in Type 2 Diabetes


Johannes F.E. Mann ... 糖尿病 • 2017.08.31
相关阅读
• 新型抗糖尿病药的心血管结局 • 应用利拉鲁肽与长期2型糖尿病患者的心血管结局

EMPA-REG OUTCOME到LEADER研究——谈降糖药物血糖控制之外的临床获益

 

殷峻†‡§¶,贾伟平†‡§¶*

†上海交通大学附属第六人民医院内分泌代谢科;‡上海市糖尿病临床医学中心;§上海市代谢病临床医学中心;¶上海市糖尿病研究所

*通讯作者

 

2015年9月17日傍晚,欧洲糖尿病研究会(EASD)年会近2万人的主会场座无虚席,来自全球的专家汇聚一堂,共同见证继UKPDS之后,糖尿病领域最重要的临床试验EMPA-REG OUTCOME结果的揭晓。当报告恩格列净使心血管死亡率降低38%时,全场掌声雷动;随后,报告人接连宣布心力衰竭住院率降低35%,全因死亡率降低32%等一个个令人目眩的结果。雷鸣般的掌声几乎连绵不绝,一直持续到发布会的结束。

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摘要


背景

在一项随机对照试验中,对于2型糖尿病合并高心血管风险并接受常规治疗的患者,我们对利拉鲁肽(一种胰高血糖素样肽1类似物)和安慰剂进行了比较,结果发现利拉鲁肽使主要终点事件(非致死性心肌梗死、非致死性卒中或心血管原因死亡)和死亡风险降低。然而,在2型糖尿病患者中,利拉鲁肽对肾脏结局的长期效果未知。

 

方法

我们在此报告该随机对照试验入组患者的预设次要肾脏结局,这些患者接受了利拉鲁肽或安慰剂治疗。次要肾脏结局为新发持续性大量白蛋白尿、持续性血清肌酐水平加倍、终末期肾脏疾病或肾脏疾病死亡构成的复合事件。肾脏结局的风险通过至事件发生时间分析,采用意向性治疗分析法得出。我们也分析了估算的肾小球滤过率和白蛋白尿的变化。

 

结果

共有9,340例患者经历了随机化,患者的中位随访期为3.84年。利拉鲁肽组与安慰剂组相比,出现肾脏结局的患者较少(4,668例利拉鲁肽组患者中有268例vs. 4,672例安慰剂组患者中有337例;风险比,0.78;95%置信区间[CI],0.67~0.92;P=0.003)。该结果主要驱动因素是,利拉鲁肽组与安慰剂组相比,较少的患者出现新发持续性大量白蛋白尿(161例 患者vs. 215例患者;风险比,0.74;95% CI,0.60~0.91;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(15.1起事件/1,000人年和16.5起事件/1,000人年),包括急性肾损伤的发生率(分别为7.1起事件/1,000人年和6.2起事件/1,000人年)。

 

结论

该预设的次要分析显示,当把利拉鲁肽与常规治疗联合使用时,与安慰剂相比,前者引起了较低的糖尿病肾脏疾病发生率和进展率(由诺和诺德和美国国立卫生研究院资助;LEADER研究在ClinicalTrials.gov注册号为NCT01179048)。





作者信息

Johannes F.E. Mann, M.D., David D. Ørsted, M.D., Ph.D., Kirstine Brown-Frandsen, M.D., Steven P. Marso, M.D., Neil R. Poulter, F.Med.Sci., Søren Rasmussen, Ph.D., Karen Tornøe, M.D., Ph.D., Bernard Zinman, M.D., and John B. Buse, M.D., Ph.D., for the LEADER Steering Committee and Investigators*
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.). Address reprint requests to Dr. Mann at the KfH Kidney Center, 15 Isoldenstr., Munich 80804, Germany, or at prof.j.mann@gmail.com. *A complete list of the steering committee and investigators in the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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