Holman Rury R, Bethel M Angelyn, Mentz Robert J, Thompson Vivian P, Lokhnygina Yuliya, Buse John B, Chan Juliana C, Choi Jasmine, Gustavson Stephanie M, Iqbal Nayyar, Maggioni Aldo P, Marso Steven P, Öhman Peter, Pagidipati Neha J, Poulter Neil, Ramachandran Ambady, Zinman Bernard, Hernandez Adrian F
From the Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford (R.R.H., M.A.B.), and the International Centre for Circulatory Health, Imperial College London, London (N.P.) - both in the United Kingdom; Duke Clinical Research Institute, Duke University School of Medicine, Durham (R.J.M., V.P.T., Y.L., N.J.P., A.F.H.), and the Division of Endocrinology, University of North Carolina School of Medicine, Chapel Hill (J.B.B.) - both in North Carolina; the Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong (J.C.C.); AstraZeneca Research and Development, Gaithersburg, MD (J.C., S.M.G., N.I., P.Ö.); Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) Research Center, Florence, Italy (A.P.M.); the Department of Cardiology, University of Texas Southwestern Medical Center, Dallas (S.P.M.); the India Diabetes Research Foundation and Dr. A. Ramachandran's Diabetes Hospitals, Chennai, India (A.R.); and the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital and University of Toronto, Toronto (B.Z.).
N Engl J Med. 2017 Sep 28;377(13):1228-1239. doi: 10.1056/NEJMoa1612917. Epub 2017 Sep 14.
The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown.
We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy.
In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups.
Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .).
在2型糖尿病患者的常规治疗基础上加用每周一次的艾塞那肽治疗对心血管系统的影响尚不清楚。
我们将有或无既往心血管疾病的2型糖尿病患者随机分组，分别接受皮下注射2mg缓释艾塞那肽或匹配的安慰剂，每周一次。主要复合结局是首次出现心血管原因死亡、非致死性心肌梗死或非致死性卒中。共同主要假设是，每周给药一次的艾塞那肽在安全性方面不劣于安慰剂，在疗效方面优于安慰剂。
总共14752例患者（其中10782例[73.1%]有既往心血管疾病）接受了中位3.2年（四分位间距为2.2至4.4年）的随访。艾塞那肽组7356例患者中有839例（11.4%；每100人年3.7次事件）发生主要复合结局事件，安慰剂组7396例患者中有905例（12.2%；每100人年4.0次事件）发生主要复合结局事件（风险比为0.91；95%置信区间[CI]为0.83至1.00），意向性分析表明，每周给药一次的艾塞那肽在安全性方面不劣于安慰剂（非劣效性P<0.001），但在疗效方面不优于安慰剂（优效性P=0.06）。两组在心血管原因死亡、致死或非致死性心肌梗死、致死或非致死性卒中、因心力衰竭住院、因急性冠状动脉综合征住院的发生率，以及急性胰腺炎、胰腺癌、甲状腺髓样癌和严重不良事件的发生率方面无显著差异。
在有或无既往心血管疾病的2型糖尿病患者中，接受艾塞那肽治疗的患者与接受安慰剂治疗的患者相比，主要不良心血管事件的发生率无显著差异。（由Amylin制药公司资助；EXSCEL临床试验注册号，NCT01144338。）
