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司美鲁肽治疗与2型糖尿病患者心血管结局关系的研究
Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes


Steven P. Marso ... 心脑血管疾病 糖尿病 • 2016.11.10

摘要


背景

监管指南规定了在2型糖尿病患者中使用新的糖尿病疗法时确认心血管安全性的必要性,以排除过多的心血管风险。司美鲁肽是一种半衰期延长至约1周的胰高血糖素样肽-1类似物,但在2型糖尿病中的心血管作用尚不清楚。

 

方法

我们将3,297例采取标准治疗方案的2型糖尿病患者随机分配接受每周一次司美鲁肽(0.5 mg或1.0 mg)或安慰剂,为期104周。主要复合结局是首次发生心血管死亡、非致死性心肌梗死或非致死性卒中。我们假设,在主要结局方面司美鲁肽应不劣于安慰剂。非劣效性界值风险比95%可信区间(CI)的上限为1.8。

 

结果

在基线时,2,735例患者(83.0%)患有已确诊的心血管疾病、慢性肾脏疾病或两者均有。在司美鲁肽组中,1,648例患者中的108例(6.6%)发生了主要结局;在安慰剂组中,1,649例患者中的146例(8.9%)发生了主要结局(风险比为0.74,95% CI为0.58~0.95,非劣效性检验P<0.001)。在接受司美鲁肽的患者中,2.9%发生了非致死性心肌梗死,而安慰剂组中的这一发生率为3.9%(风险比为0.74,95% CI为0.51~1.08,P=0.12);司美鲁肽组和安慰剂组中非致死性卒中的发生率分别为1.6%和2.7%(风险比为0.61,95% CI为0.38~0.99,P=0.04)。两组中因心血管原因导致的死亡率相近。司美鲁肽组中新发或恶化的肾病的发生率更低,但是视网膜病变并发症(玻璃体积血、失明或其他需要使用玻璃体内药物或光凝治疗的疾病)显著更高(风险比为1.76,95% CI为1.11~2.78,P=0.02)。司美鲁肽组中发生的严重不良事件数目较少,但有更多的患者由于不良事件——主要是胃肠道事件——而停止了治疗。

 

结论

在具有高心血管风险的2型糖尿病患者中,接受司美鲁肽的患者与接受安慰剂的患者相比,其心血管死亡、非致死性心肌梗死或非致死性卒中的发生率显著降低,这一结局证实了司美鲁肽的非劣效性(研究由诺和诺德公司[Novo Nordisk]资助,SUSTAIN-6在ClinicalTrials.gov注册号为NCT01720446)。





作者信息

Steven P. Marso, M.D., Stephen C. Bain, M.D., Agostino Consoli, M.D., Freddy G. Eliaschewitz, M.D., Esteban Jódar, M.D., Lawrence A. Leiter, M.D., Ildiko Lingvay, M.D., M.P.H., M.S.C.S., Julio Rosenstock, M.D., Jochen Seufert, M.D., Ph.D., Mark L. Warren, M.D., Vincent Woo, M.D., Oluf Hansen, M.Sc., Anders G. Holst, M.D., Ph.D., Jonas Pettersson, M.D., Ph.D., and Tina Vilsbøll, M.D., D.M.Sc., for the SUSTAIN-6 Investigators*
From the Research Medical Center, Kansas City, MO (S.P.M.); School of Medicine, Swansea University, Swansea, United Kingdom (S.C.B.); Department of Medicine and Aging Science and Center of Excellence on Aging and Translational Medicine, G. d’Annunzio University, Chieti-Pescara, Italy (A.C.); CPClin Research Center/Hospital Israelita Albert Einstein, São Paulo (F.G.E.); Hospital Universitario Quirón Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid (E.J.); Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, University of Toronto, Toronto (L.A.L.), and the University of Manitoba, Winnipeg (V.W.) — both in Canada; University of Texas Southwestern Medical Center (I.L.) and Dallas Diabetes Research Center at Medical City (J.R.) — both in Dallas; University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (J.S.); Physicians East, Greenville, NC (M.L.W.); and Novo Nordisk, Søborg (O.H., A.G.H., J.P.), and the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup (T.V.) — both in Denmark.Address reprint requests to Dr. Marso at Cardiovascular Services, HCA Midwest Health, Research Medical Center, 2316 E. Meyer Blvd., Kansas City, MO 64132, or at smarso@gmail.com. *A complete list of the investigators in the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6) is provided in the Supplementary Appendix, available at NEJM.org.

 

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