Calhoun Cardiology Center, Department of Medicine, University of Connecticut School of Medicine, 263 Farmington Ave., Farmington, CT 06030-3940, USA.
N Engl J Med. 2013 Oct 3;369(14):1327-35. doi: 10.1056/NEJMoa1305889. Epub 2013 Sep 2.
To assess potentially elevated cardiovascular risk related to new antihyperglycemic drugs in patients with type 2 diabetes, regulatory agencies require a comprehensive evaluation of the cardiovascular safety profile of new antidiabetic therapies. We assessed cardiovascular outcomes with alogliptin, a new inhibitor of dipeptidyl peptidase 4 (DPP-4), as compared with placebo in patients with type 2 diabetes who had had a recent acute coronary syndrome.
We randomly assigned patients with type 2 diabetes and either an acute myocardial infarction or unstable angina requiring hospitalization within the previous 15 to 90 days to receive alogliptin or placebo in addition to existing antihyperglycemic and cardiovascular drug therapy. The study design was a double-blind, noninferiority trial with a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.
A total of 5380 patients underwent randomization and were followed for up to 40 months (median, 18 months). A primary end-point event occurred in 305 patients assigned to alogliptin (11.3%) and in 316 patients assigned to placebo (11.8%) (hazard ratio, 0.96; upper boundary of the one-sided repeated confidence interval, 1.16; P<0.001 for noninferiority). Glycated hemoglobin levels were significantly lower with alogliptin than with placebo (mean difference, -0.36 percentage points; P<0.001). Incidences of hypoglycemia, cancer, pancreatitis, and initiation of dialysis were similar with alogliptin and placebo.
Among patients with type 2 diabetes who had had a recent acute coronary syndrome, the rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin as compared with placebo. (Funded by Takeda Development Center Americas; EXAMINE ClinicalTrials.gov number, NCT00968708.).
为了评估 2 型糖尿病患者新的抗高血糖药物可能存在的心血管风险，监管机构要求对新的抗糖尿病治疗药物的心血管安全性进行全面评估。我们评估了新型二肽基肽酶-4（DPP-4）抑制剂阿格列汀与安慰剂相比，在近期发生急性冠脉综合征的 2 型糖尿病患者中的心血管结局。
我们将近期发生急性心肌梗死或不稳定型心绞痛需要住院治疗的 2 型糖尿病患者随机分配，在接受现有降糖和心血管药物治疗的基础上，加用阿格列汀或安慰剂。该研究设计为双盲、非劣效性试验，主要终点为心血管死亡、非致死性心肌梗死或非致死性卒中复合终点的风险比预设非劣效性界值为 1.3。
共 5380 例患者接受了随机分组，随访时间最长达 40 个月（中位数 18 个月）。阿格列汀组 305 例患者（11.3%）和安慰剂组 316 例患者（11.8%）发生主要终点事件（风险比，0.96；单侧重复置信区间上限，1.16；P<0.001，非劣效性检验）。阿格列汀组的糖化血红蛋白水平显著低于安慰剂组（平均差值，-0.36 个百分点；P<0.001）。低血糖、癌症、胰腺炎和开始透析的发生率在阿格列汀组和安慰剂组相似。
在近期发生急性冠脉综合征的 2 型糖尿病患者中，与安慰剂相比，DPP-4 抑制剂阿格列汀并未增加主要不良心血管事件的发生率。（由武田药品工业株式会社开发中心美洲分部资助；EXAMINE 临床试验.gov 编号，NCT00968708）。
