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卡格列净与2型糖尿病合并肾病患者的肾脏结局之间的关系
Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy


Vlado Perkovic ... 糖尿病 • 2019.06.13
NEJM 动画解读

卡格列净治疗2型糖尿病
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• 卡格列净治疗2型糖尿病的心血管和肾脏事件风险研究 • 卡格列净与非钠-葡萄糖协同转运蛋白-2抑制剂类抗糖尿病药对心血管结局的影响比较 • 卡格列净作为2型糖尿病患者的一级预防和二级预防都有效

摘要


背景

在全球范围内,2型糖尿病是肾衰竭的主要原因,但有效的长期疗法很少。在钠-葡萄糖协同转运蛋白-2(SGLT2)抑制剂的心血管试验中,探索性结果提示此类药物可能改善2型糖尿病患者的肾脏结局。

 

方法

在这项双盲、随机试验中,我们将2型糖尿病合并蛋白尿性慢性肾脏病患者随机分组,分别接受每日100 mg卡格列净(口服SGLT2抑制剂)或安慰剂治疗。所有患者均符合以下条件:肾小球滤过率(GFR)估计值为30~<90 mL/(1.73 m2·min),有白蛋白尿(白蛋白[mg]与肌酐[g]的比值,>300~5000),并接受肾素-血管紧张素系统阻滞疗法。主要结局是由终末期肾脏病(透析、移植或GFR估计值持续<15 mL/[1.73 m2·min])、血清肌酐水平加倍或者肾脏或心血管原因死亡构成的复合结局。我们对预设的次要结局进行了分级检验。

 

结果

计划的期中分析完成之后,按照数据和安全监察委员会的建议,我们提前终止了试验。当时有4,401例患者已随机分组,中位随访时间为2.62年。卡格列净组中主要结局的相对风险比安慰剂组低30%,两组的事件发生率分别为43.2起/1,000患者-年和61.2起/1,000患者-年(风险比,0.70;95%置信区间[CI],0.59~0.82;P=0.00001)。卡格列净组中由终末期肾脏病、肌酐水平加倍或肾脏原因死亡构成的肾脏复合结局的相对风险比安慰剂组低34%(风险比,0.66;95% CI,0.53~0.81;P<0.001),终末期肾脏病的相对风险比安慰剂组低32%(风险比,0.68;95% CI,0.54~0.86;P=0.002)。卡格列净组中心血管死亡、心肌梗死或卒中(风险比,0.80;95% CI,0.67~0.95;P=0.01)以及心力衰竭住院(风险比,0.61;95% CI,0.47~0.80;P<0.001)的风险也较低。两组的截肢或骨折发生率无显著差异。

 

结论

在2型糖尿病合并肾脏病患者中,在中位2.62年随访时,卡格列净组的肾衰竭和心血管事件风险低于安慰剂组(由Janssen Research and Development资助;CREDENCE在ClinicalTrials.gov注册号为NCT02065791)。





作者信息

Vlado Perkovic, M.B., B.S., Ph.D., Meg J. Jardine, M.B., B.S., Ph.D., Bruce Neal, M.B., Ch.B., Ph.D., Severine Bompoint, B.Sc., Hiddo J.L. Heerspink, Pharm.D., Ph.D., David M. Charytan, M.D., Robert Edwards, M.P.H., Rajiv Agarwal, M.D., George Bakris, M.D., Scott Bull, Pharm.D., Christopher P. Cannon, M.D., George Capuano, Ph.D., Pei-Ling Chu, Ph.D., Dick de Zeeuw, M.D., Ph.D., Tom Greene, Ph.D., Adeera Levin, M.D., Carol Pollock, M.B., B.S., Ph.D., David C. Wheeler, M.D., Yshai Yavin, M.B., Ch.B., Hong Zhang, M.D., Ph.D., Bernard Zinman, M.D., Gary Meininger, M.D., Barry M. Brenner, M.D., and Kenneth W. Mahaffey, M.D. for the CREDENCE Trial Investigators*
From the George Institute for Global Health, University of New South Wales Sydney (V.P., M.J.J., B.N., S. Bompoint), the Royal North Shore Hospital (V.P.), Concord Repatriation General Hospital (M.J.J.), and the Charles Perkins Centre, University of Sydney (B.N.), Sydney, and the Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Royal North Shore Hospital, St. Leonards, NSW (C.P.) — all in Australia; Imperial College London (B.N.) and the Department of Renal Medicine, UCL Medical School (D.C.W.) — both in London; the Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands (H.J.L.H., D.Z.); the Nephrology Division, NYU School of Medicine and NYU Langone Medical Center, New York (D.M.C.); Baim Institute for Clinical Research (D.M.C., C.P.C., B.M.B.), the Cardiovascular Division (C.P.C.) and the Renal Division and Department of Medicine (B.M.B), Brigham and Women’s Hospital, and Harvard Medical School (B.M.B.) — all in Boston; Janssen Research and Development, Raritan, NJ (R.E., S. Bull, G.C., P.-L.C., Y.Y., G.M.); Indiana University School of Medicine and Veterans Affairs Medical Center, Indianapolis (R.A.); the Department of Medicine, University of Chicago Medicine, Chicago (G.B.); the Division of Biostatistics, Department of Population Health Sciences, University of Utah, Salt Lake City (T.G.); the Division of Nephrology, University of British Columbia, Vancouver (A.L.), and the Lunenfeld–Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto (B.Z.) — all in Canada; the Renal Division, Peking University First Hospital, Beijing (H.Z.); and the Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA (K.W.M.). Address reprint requests to Dr. Perkovic at the George Institute for Global Health, University of New South Wales Sydney, Level 5, 1 King St., Newtown, NSW 2042, Australia, or at vperkovic@georgeinstitute.org.au. *A complete list of the CREDENCE trial investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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