Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes.
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes.
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DOI：
10.1056/nejmoa1603827
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发表时间：
2016-07-28
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影响因子：
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通讯作者：
LEADER Trial Investigators
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作者：
Marso SP;Daniels GH;Brown-Frandsen K;Kristensen P;Mann JF;Nauck MA;Nissen SE;Pocock S;Poulter NR;Ravn LS;Steinberg WM;Stockner M;Zinman B;Bergenstal RM;Buse JB;LEADER Steering Committee;LEADER Trial Investigators
Liraglutide（一种胰高血糖素样肽1类似物）的心血管效应在2型糖尿病患者的标准护理中添加时，仍然未知。
在这项双盲试验中，我们随机分配了患有2型糖尿病的患者，并且患有高liraglutide或安慰剂的心血管风险高。事件时间分析中的主要综合结果是心血管原因，非致命性心肌梗塞或非致命性中风的死亡首次出现。主要的假设是，利拉格林在主要结局方面将不适合安慰剂，危险比的95％置信区间的上边界的边界为1.30。没有针对预定的探索结果进行多重调整。
共有9340名患者进行了随机分组。中位随访时间为3。8年。在Liraglutide组（4668例患者中有608例）比安慰剂组（4672 [4672 [14.9％]中的694例[14.9％]）（危险比，0.87; 95％置信区间[CI]，0.78至0.97; P <0.001 for NonInInity; P = 0.01）。在Liraglutide组（219例患者[4.7％]）中，因心血管原因的患者少于安慰剂组（278 [6.0％]）（危险比，0.78; 95％CI，0.66至0.93; p = 0.007）。 Liraglutide组（381例患者[8.2％]）的死亡率低于安慰剂组（447 [9.6％]）（危险比，0.85; 95％CI，0.74至0.97至0.97; P = 0.02）。 Liraglutide组的非致命心肌梗塞，非致命性中风和心力衰竭的住院率比安慰剂组低。导致Liraglutide停用的最常见不良事件是胃肠道事件。 Liraglutide组的胰腺炎发病率比安慰剂组低。
在事件发生的分析中，与安慰剂相比，甲中西酯的患者对心血管原因，非致命性心肌梗死或非致命性中风的死亡率低于安慰剂。 （由Novo Nordisk和国立卫生研究院资助； Leader Clinicaltrials.gov编号，NCT01179048。）
The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P =0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group. In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048.)