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口服司美鲁肽与2型糖尿病患者的心血管结局
Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes


Mansoor Husain ... 糖尿病 • 2019.08.29
相关阅读
• 司美鲁肽治疗与2型糖尿病患者心血管结局关系的研究 • 口服司美鲁肽治疗心血管高危的2型糖尿病患者

摘要


背景

确定2型糖尿病新疗法的心血管安全性具有重要意义。目前已有胰高血糖素样肽-1受体激动剂司美鲁肽(semaglutide)皮下给药剂型的安全性数据,但我们还需要司美鲁肽口服剂型的安全性数据。

 

方法

我们在心血管风险高的患者(年龄≥50岁并且患心血管疾病或慢性肾脏病,或者年龄≥60岁并且仅有心血管危险因素)中开展了一项事件驱动的随机、双盲、安慰剂对照试验,试验中评估了患者每日1次口服司美鲁肽的心血管结局。在至事件发生的时间分析中,主要结局是首次发生主要心血管不良事件(心血管原因死亡、非致死性心肌梗死或非致死性卒中)。本试验旨在排除相对于安慰剂而言80%的心血管超额危险度(对于主要结局风险比的95%置信区间上限,非劣效性界值为1.8)。

 

结果

共有3,183例患者被随机分配接受口服司美鲁肽或安慰剂治疗。患者平均年龄为66岁;2,695例患者(84.7%)≥50岁并且患心血管疾病或慢性肾脏病。患者参与试验的中位时间长度为15.9个月。口服司美鲁肽组1,591例患者中的61例(3.8%)和安慰剂组1,592例患者中的76例(4.8%)发生了主要心血管不良事件(风险比,0.79;95%置信区间[CI],0.57~1.11;对于非劣效性,P<0.001)。主要结局各构成部分的结果如下:心血管原因死亡,口服司美鲁肽组1,591例患者中的15例(0.9%)和安慰剂组1,592例患者中的30例(1.9%)(风险比,0.49;95% CI,0.27~0.92);非致死性心肌梗死,分别为1,591例患者中的37例(2.3%)和1,592例患者中的31例(1.9%)(风险比,1.18;95% CI,0.73~1.90);非致死性卒中,分别为1,591例患者中的12例(0.8%)和1,592例患者中的16例(1.0%)(风险比,0.74;95% CI,0.35~1.57)。口服司美鲁肽组1,591例患者中的23例(1.4%)和安慰剂组1,592例患者中的45例(2.8%)死亡(风险比,0.51;95% CI,0.31~0.84)。导致停用试验药物(口服司美鲁肽或安慰剂)的胃肠道不良事件在口服司美鲁肽组中较常见。

 

结论

在这项对2型糖尿病患者开展的试验中,口服司美鲁肽的心血管风险不劣于安慰剂(由诺和诺德公司资助;PIONEER 6在ClinicalTrials.gov注册号为NCT02692716)。





作者信息

Mansoor Husain, M.D., Andreas L. Birkenfeld, M.D., Morten Donsmark, Ph.D., Kathleen Dungan, M.D., M.P.H., Freddy G. Eliaschewitz, M.D., Denise R. Franco, M.D., Ole K. Jeppesen, M.Sc., Ildiko Lingvay, M.D., M.P.H., M.S.C.S., Ofri Mosenzon, M.D., Sue D. Pedersen, M.D., Cees J. Tack, M.D., Mette Thomsen, M.D., D.M.Sc., Tina Vilsbøll, M.D., D.M.Sc., Mark L. Warren, M.D., and Stephen C. Bain, M.D. for the PIONEER 6 Investigators*
From the Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto (M.H.), and the C-endo Diabetes and Endocrinology Clinic, Calgary, AB (S.D.P.) — all in Canada; Medical Clinic III, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum München at Technische Universität Dresden, German Center for Diabetes Research, Dresden, Germany (A.L.B.); the Division of Diabetes and Nutritional Sciences, Rayne Institute, King’s College London, London (A.L.B.), and the Diabetes Research Unit Cymru, Swansea University Medical School, Swansea (S.C.B.) — both in the United Kingdom; Novo Nordisk, Søborg, Denmark (M.D., O.K.J., M.T.); the Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (K.D.); Centro de Pesquisas Clínicas/Diagnosticos da America Clinical Research Center, São Paulo (F.G.E., D.R.F.); the Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem (O.M.); the Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (C.J.T); Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark (T.V.); and Physicians East, Greenville, NC (M.L.W.). Address reprint requests to Dr. Husain at Toronto General Hospital, 101 College St., Rm. 3-909, Toronto, ON M5G 1L7, Canada, or at mansoor.husain@uhn.ca. *A complete list of investigators in the PIONEER 6 trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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