皮下注射艾塞那肽与2型糖尿病的心血管结局：一项非劣效性随机对照试验-小柯机器人-科学网

皮下注射艾塞那肽与2型糖尿病的心血管结局：一项非劣效性随机对照试验

2021-12-11 11:04

美国布列根和妇女医院Christian T. Ruff等研究人员完成皮下注射艾塞那肽与2型糖尿病的心血管结局：一项非劣效性随机对照试验。2021年12月6日，《自然—医学》杂志在线发表了这项成果。

研究人员表示，定期注射的胰高血糖素样肽1受体激动剂（GLP-1RA）已被证明不会增加，而且对于该类药物的某些成员来说，会降低心血管事件的风险。持续皮下输注GLP-1RA艾塞那肽（ITCA 650）的心血管安全性尚不清楚。

研究人员随机分配了患有或面临动脉粥样硬化性心血管疾病（ASCVD）风险的2型糖尿病患者接受ITCA 650或安慰剂，以评估批准前试验（NCT01455896）的心血管安全性。主要结果是心血管死亡、非致命性心肌梗死、非致命性中风或因不稳定心绞痛住院的综合结果。根据美国食品和药物管理局2008年的指导意见，危险比（HR）的95%置信区间（CI）的上限采用了1.8的非劣效边际。研究人员对4,156名患者进行了随机分组（其中2075人被分配接受ITCA 650，2,081人被分配接受安慰剂），这些患者的随访时间中位数为16个月。ITCA 650组有4.6%（95/2,075）的患者出现主要结果，安慰剂组有3.8%（79/2,081）的患者出现主要结果，符合预先指定的非劣效性标准（HR=1.21，95%CI，0.90-1.63，P_{non-inferiority}=0.004）。

两组之间的严重不良事件相似。ITCA 650组的不良事件（72%，1,491/2,074）比安慰剂组（63.9%，1,325/2,070）更频繁，主要是由于服用ITCA 650时胃肠道事件和紊乱增加。在患有ASCVD或有ASCVD风险的2型糖尿病患者中，ITCA 650的疗效不逊于安慰剂。需要进行更大规模和更长时间的心血管结果试验，以更精确地确定ITCA 650对这一人群的心血管影响。

附：英文原文

Title: Subcutaneous infusion of exenatide and cardiovascular outcomes in type 2 diabetes: a non-inferiority randomized controlled trial

Author: Ruff, Christian T., Baron, Michelle, Im, KyungAh, ODonoghue, Michelle L., Fiedorek, Fred T., Sabatine, Marc S.

Issue&Volume: 2021-12-06

Abstract: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) injected periodically have been shown to not increase and, for some members of this class, decrease the risk of cardiovascular events. The cardiovascular safety of delivering a continuous subcutaneous infusion of the GLP-1RA exenatide (ITCA 650) is unknown. Here, we randomly assigned patients with type 2 diabetes with, or at risk for, atherosclerotic cardiovascular disease (ASCVD) to receive ITCA 650 or placebo to assess cardiovascular safety in a pre-approval trial (NCT01455896). The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for unstable angina. On the basis of 2008 guidance from the US Food and Drug Administration, a non-inferiority margin of 1.8 for the upper bound of the 95% confidence interval (CI) of the hazard ratio (HR) was used. We randomized 4,156 patients (2,075 assigned to receive ITCA 650 and 2,081 assigned to receive placebo) who were followed for a median of 16 months. The primary outcome occurred in 4.6% (95/2,075) of patients in the ITCA 650 group and 3.8% (79/2,081) of patients in the placebo group, meeting the pre-specified non-inferiority criterion (HR = 1.21, 95% CI, 0.90–1.63, Pnon-inferiority=0.004). Serious adverse events were similar between the two groups. Adverse events were more frequent in the ITCA 650 group (72%, 1,491/2,074) than in the placebo group (63.9%, 1,325/2,070), mainly due to an increase in gastrointestinal events and disorders while on ITCA 650. In patients with type 2 diabetes with, or at risk for, ASCVD, ITCA 650 was non-inferior to placebo. A larger and longer-duration cardiovascular outcomes trial is needed to define more precisely the cardiovascular effects of ITCA 650 in this population.

DOI: 10.1038/s41591-021-01584-3

Source: https://www.nature.com/articles/s41591-021-01584-3

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex

本期文章：《自然—医学》：Online/在线发表

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