Merck & Co., Inc., Kenilworth, NJ, USA.
Merck & Co., Inc., RY34-A260, P.O. Box 2000, Rahway, NJ, 07065, USA.
Cardiovasc Diabetol. 2017 Sep 11;16(1):112. doi: 10.1186/s12933-017-0593-8.
Omarigliptin is a once-weekly (q.w.) oral DPP-4 inhibitor that is approved for the treatment of patients with type 2 diabetes mellitus (T2DM) in Japan. To support approval of omarigliptin in the United States, the clinical development program included a cardiovascular (CV) safety study. Subsequently, a business decision was made not to submit a marketing application for omarigliptin in the United States, and the CV safety study was terminated. Herein we report an analysis of data from that early-terminated study.
In this randomized, double-blind study, 4202 patients with T2DM and established CV disease were assigned to either omarigliptin 25 mg q.w. or matching placebo in addition to their existing diabetes therapy. A Cox proportional hazards model was used to summarize the primary endpoint of time to first major adverse CV event (MACE, the composite of CV death, nonfatal myocardial infarction, and nonfatal stroke) and the analysis of first event of hospitalization for heart failure (hHF).
The median follow-up was approximately 96 weeks (range 1.1-178.6 weeks). The primary MACE outcome occurred in 114/2092 patients in the omarigliptin group (5.45%; 2.96/100 patient-years) and 114/2100 patients in the placebo group (5.43%; 2.97/100 patient-years), with a hazard ratio (HR) of 1.00 (95% confidence interval [CI] 0.77, 1.29). The hHF outcome occurred in 20/2092 patients in the omarigliptin group (0.96%; 0.51/100 patient-years) and 33/2100 patients in the placebo group (1.57%; 0.85/100 patient-years), with an HR of 0.60 (95% CI 0.35, 1.05). After 142 weeks, the least-squares mean difference (omarigliptin vs. placebo) in glycated hemoglobin levels was -0.3% (95% CI -0.46, -0.14). The numbers of patients with adverse events, serious adverse events or discontinued from study medication due to adverse events were similar in the omarigliptin and placebo groups.
In this CV safety study of patients with T2DM and established CV disease, omarigliptin did not increase the risk of MACE or hHF and was generally well tolerated. Trial registration ClinicalTrials.gov: NCT01703208. Registered 05 October 2012.
奥马利格列汀是一种每周一次（qw）的口服 DPP-4 抑制剂，在日本被批准用于治疗 2 型糖尿病（T2DM）患者。为了支持奥马利格列汀在美国的批准，临床开发项目包括一项心血管（CV）安全性研究。随后，公司做出了不在美国提交奥马利格列汀上市申请的商业决策，该 CV 安全性研究也随之终止。在此，我们报告该提前终止研究的数据分析结果。
在这项随机、双盲研究中，4202 名患有 T2DM 且伴有已确诊心血管疾病的患者被随机分配至奥马利格列汀 25mgqw 组或匹配安慰剂组，同时接受其现有糖尿病治疗。采用 Cox 比例风险模型总结主要终点（首次发生主要心血管不良事件[MACE]，即心血管死亡、非致死性心肌梗死和非致死性卒中的复合终点）和因心力衰竭（HF）住院的首次事件（hHF）的分析结果。
中位随访时间约为 96 周（范围 1.1-178.6 周）。奥马利格列汀组 114/2092 例（5.45%；2.96/100 患者-年）和安慰剂组 114/2100 例（5.43%；2.97/100 患者-年）患者发生首次 MACE 事件，风险比（HR）为 1.00（95%置信区间[CI]0.77，1.29）。奥马利格列汀组 20/2092 例（0.96%；0.51/100 患者-年）和安慰剂组 33/2100 例（1.57%；0.85/100 患者-年）患者发生首次 hHF 事件，HR 为 0.60（95% CI 0.35，1.05）。治疗 142 周后，奥马利格列汀组与安慰剂组之间糖化血红蛋白水平的最小二乘均值差异为-0.3%（95% CI-0.46，-0.14）。奥马利格列汀组和安慰剂组发生不良事件、严重不良事件或因不良事件而停药的患者数量相似。
在这项伴有已确诊心血管疾病的 T2DM 患者的 CV 安全性研究中，奥马利格列汀未增加 MACE 或 hHF 的风险，且总体耐受性良好。
ClinicalTrials.gov：NCT01703208。注册日期：2012 年 10 月 5 日。
