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达格列净用于2型糖尿病患者的心血管结局
Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes


Stephen D. Wiviott ... 糖尿病 • 2019.01.24
相关阅读
• SGLT2抑制剂的心血管作用 • 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 • 卡格列净治疗2型糖尿病的心血管和肾脏事件风险研究 • 卡格列净相关的糖尿病酮症酸中毒

摘要


背景

达格列净是促进2型糖尿病患者尿液中葡萄糖排泄的钠-葡萄糖协同转运蛋白2(SGLT2)选择性抑制剂,其心血管安全性尚未明确。

 

方法

我们将患动脉粥样硬化性心血管疾病或有患病风险的2型糖尿病患者随机分组,分别接受达格列净或安慰剂治疗。主要的安全性结局是由主要心血管不良事件(MACE)组成的复合结局,MACE的定义为心血管原因死亡、心肌梗死或缺血性卒中。主要疗效结局是MACE以及由心血管原因死亡或心力衰竭住院组成的复合结局。次要疗效结局是肾脏复合结局(估计肾小球滤过率降低≥40%且降至<60 mL/[1.73m2·min]、新发终末期肾疾病或者肾脏或心血管原因死亡)和全因死亡。

 

结果

我们评估了17,160例患者,包括10,186例未患动脉粥样硬化性心血管疾病的患者,中位随访期为4.2年。在主要安全性结局分析中,达格列净与安慰剂相比,在MACE方面达到预设的非劣效性标准(95%置信区间[CI]上界,<1.3;非劣效性P<0.001)。在两项主要疗效分析中,达格列净未达到较低的MACE发生率(达格列净组8.8%,安慰剂组9.4%;风险比,0.93;95% CI,0.84~1.03;P=0.17),但的确达到了较低的心血管原因死亡或心力衰竭住院发生率(4.9% vs. 5.8%;风险比,0.83;95% CI,0.73~0.95;P=0.005),这反映了较低的心力衰竭住院发生率(风险比,0.73;95% CI,0.61~0.88);心血管原因死亡无组间差异(风险比,0.98;95% CI,0.82~1.17)。达格列净组和安慰剂组的肾脏事件发生率分别为4.3%和5.6%(风险比,0.76;95% CI,0.67~0.87),全因死亡率分别为6.2%和6.6%(风险比,0.93;95% CI,0.82~1.04)。达格列净组的糖尿病酮症酸中毒发生率高于安慰剂组(0.3% vs. 0.1%,P=0.02),导致停药或被视为严重不良事件的生殖器感染发生率也是达格列净组高于安慰剂组(0.9% vs. 0.1%,P<0.001)。

 

结论

在患动脉粥样硬化性心血管疾病或有患病风险的2型糖尿病患者中,达格列净治疗后的MACE发生率未高于,也未低于安慰剂治疗,但达格列净的确达到了较低的心血管原因死亡或心力衰竭住院发生率,这一发现反映了较低的心力衰竭住院发生率(由阿斯利康资助;DECLARE–TIMI 58在ClinicalTrials.gov注册号为NCT01730534)。





作者信息

Stephen D. Wiviott, M.D., Itamar Raz, M.D., Marc P. Bonaca, M.D., M.P.H., Ofri Mosenzon, M.D., Eri T. Kato, M.D., M.P.H., Ph.D., Avivit Cahn, M.D., Michael G. Silverman, M.D., M.P.H., Thomas A. Zelniker, M.D., Julia F. Kuder, M.A., Sabina A. Murphy, M.P.H., Deepak L. Bhatt, M.D., M.P.H., Lawrence A. Leiter, M.D., Darren K. McGuire, M.D., John P.H. Wilding, M.D., Christian T. Ruff, M.D., M.P.H., Ingrid A.M. Gause-Nilsson, M.D., Ph.D., Martin Fredriksson, M.D., Ph.D., Peter A. Johansson, M.Sc., Anna-Maria Langkilde, M.D., Ph.D., and Marc S. Sabatine, M.D., M.P.H. for the DECLARE–TIMI 58 Investigators*
From the Thrombolysis in Myocardial Infarction (TIMI) Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital (S.D.W., M.P.B., T.A.Z., J.F.K., S.A.M., D.L.B., C.T.R., M.S.S.), and the Cardiology Division, Massachusetts General Hospital (M.G.S.) — both in Boston; the Diabetes Unit, Hadassah Hebrew University Hospital, Jerusalem (I.R., O.M., A.C.); the Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan (E.T.K.); Li Ka Shing Knowledge Institute, St. Michael’s Hospital, University of Toronto, Toronto (L.A.L.); the Division of Cardiology, University of Texas Southwestern Medical Center, Dallas (D.K.M.); Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom (J.P.H.W.); and AstraZeneca Gothenburg, Mölndal, Sweden (I.A.M.G.-N., M.F., P.A.J., A.-M.L.). Address reprint requests to Dr. Wiviott at the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Hale Building for Transformative Medicine, 60 Fenwood Rd., 7th Fl., Boston, MA 02115, or at swiviott@bwh.harvard.edu. *A complete list of the DECLARE–TIMI 58 investigators and executive committee and steering committee members is provided in the Supplementary Appendix, available at NEJM.org.

 

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