A randomized, placebo-controlled study of the cardiovascular safety of the once-weekly DPP-4 inhibitor omarigliptin in patients with type 2 diabetes mellitus.
A randomized, placebo-controlled study of the cardiovascular safety of the once-weekly DPP-4 inhibitor omarigliptin in patients with type 2 diabetes mellitus.
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DOI：
10.1186/s12933-017-0593-8
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发表时间：
2017-09-11
影响因子：
9.3
通讯作者：
Lai E
中科院分区：
文献类型：
--
作者：
Gantz I;Chen M;Suryawanshi S;Ntabadde C;Shah S;O'Neill EA;Engel SS;Kaufman KD;Lai E
奥格列汀是一种每周一次 (q.w.) 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。为了支持奥格列汀在美国获得批准，临床开发计划包括一项心血管（CV）安全性研究。随后，商业决定不再提交奥格列汀在美国的上市申请，CV安全性研究也终止。在此，我们报告了对该早期终止的研究的数据分析。在这项随机、双盲研究中，4202 名患有 T2DM 并确诊有心血管疾病的患者被分配服用奥格列汀 25 毫克每日一次和每周 25 毫克。或除了现有的糖尿病治疗之外还使用匹配的安慰剂。使用 Cox 比例风险模型总结首次主要不良心血管事件（MACE，心血管死亡、非致死性心肌梗死和非致死性中风的复合）时间的主要终点，并分析首次因心力衰竭 (hHF) 住院的事件。中位随访时间约为 96 周（范围 1.1-178.6 周）。主要 MACE 结局发生在奥格列汀组的 114/2092 名患者（5.45%；2.96/100 患者年）和安慰剂组的 114/2100 名患者（5.43%；2.97/100 患者年），风险比 (HR) 为 1.00（95% 置信区间 [CI] 0.77， 1.29）。奥格列汀组有 20/2092 名患者（0.96%；0.51/100 患者年）发生 hHF 结局，安慰剂组有 33/2100 名患者（1.57%；0.85/100 患者年）发生 hHF，HR 为 0.60（95% CI 0.35，1.05）。 142 周后，糖化血红蛋白水平的最小二乘平均差（奥格列汀与安慰剂）为 -0.3% (95% CI -0.46, -0.14)。奥格列汀组和安慰剂组中出现不良事件、严重不良事件或因不良事件而停止研究药物的患者数量相似。在这项针对 T2DM 和已确诊的 CV 疾病患者的 CV 安全性研究中，奥格列汀不会增加 MACE 或 hHF 的风险，并且总体耐受性良好。 试验注册 ClinicalTrials.gov：NCT01703208。注册日期：2012 年 10 月 5 日 本文的在线版本 (doi:10.1186/s12933-017-0593-8) 包含补充材料，可供授权用户使用。
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 The online version of this article (doi:10.1186/s12933-017-0593-8) contains supplementary material, which is available to authorized users.
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影响因子：
158.5
作者：
Scirica, Benjamin M.;Bhatt, Deepak L.;Simmons, D.
通讯作者：
Simmons, D.
影响因子：
5.8
作者：
Hermansen, K.;Kipnes, M.;Stein, P.
通讯作者：
Stein, P.
DOI：
10.1111/dom.12832
发表时间：
2017-03
期刊：
Diabetes, obesity & metabolism
影响因子：
--
作者：
Goldenberg R;Gantz I;Andryuk PJ;O'Neill EA;Kaufman KD;Lai E;Wang YN;Suryawanshi S;Engel SS
通讯作者：
Engel SS
DOI：
10.1056/nejmoa1305889
发表时间：
2013-10-03
期刊：
The New England journal of medicine
影响因子：
--
作者：
White, William B;Cannon, Christopher P;Zannad, Faiez
通讯作者：
Zannad, Faiez
DOI：
10.1111/dom.12988
发表时间：
2017-11
期刊：
Diabetes, obesity & metabolism
影响因子：
--
作者：
Gantz I;Okamoto T;Ito Y;Okuyama K;O'Neill EA;Kaufman KD;Engel SS;Lai E;the Omarigliptin Study 020 Group
通讯作者：
the Omarigliptin Study 020 Group