小柯机器人

澳大利亚蒙纳士大学Sophia Zoungas、英国格拉斯哥大学Naveed Sattar等研究人员合作完成tirzepatide的心血管事件风险评估。这一研究成果于2022年2月24日在线发表在国际学术期刊《自然—医学》上。

研究人员表示，tirzepatide是一种新型的、每周一次的GIP/GLP-1双受体激动剂，正在开发用于治疗2型糖尿病（T2D）和肥胖症。它与心血管结果的关系需要评估。

这项预先指定的心血管荟萃分析包括tirzepatide T2D临床开发项目SURPASS的所有7项持续时间至少26周的随机对照试验。该荟萃分析的预设主要目标是比较汇集的tirzepatide组和对照组之间首次发生确认的四种主要不良心血管事件（MACE-4；心血管死亡、心肌梗死、中风和住院不稳定心绞痛）的时间。分层的Cox比例危害模型，以治疗为固定效应，以试验水平的心血管风险为分层因素，用于估计tirzepatide与对照组的危险比（HR）和置信区间（CI）。分析了4887名接受tirzepatide治疗的参与者和2328名对照组参与者的数据。

总的来说，142名参与者，其中109名来自高心血管风险的试验，33名来自低心血管风险的六个试验，至少有一个MACE-4事件。tirzepatide与对照组相比，MACE-4的HR为0.80（95%CI，0.57-1.11）；心血管死亡为0.90（95%CI，0.50-1.61）；全因死亡为0.80（95%CI，0.51-1.25）。在任何亚组中都没有观察到效果修正的证据，尽管对于心血管高风险的参与者来说，证据更为有力。在T2D参与者与对照组相比，tirzepatide并没有增加主要心血管事件的风险。

附：英文原文

Title: Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis

Author: Sattar, Naveed, McGuire, Darren K., Pavo, Imre, Weerakkody, Govinda J., Nishiyama, Hiroshi, Wiese, Russell J., Zoungas, Sophia

Issue&Volume: 2022-02-24

Abstract: Tirzepatide is a novel, once weekly, dual GIP/GLP-1 receptor agonist and is under development for the treatment of type 2 diabetes (T2D) and obesity. Its association with cardiovascular outcomes requires evaluation. This pre-specified cardiovascular meta-analysis included all seven randomized controlled trials with a duration of at least 26 weeks from the tirzepatide T2D clinical development program, SURPASS. The pre-specified primary objective of this meta-analysis was the comparison of the time to first occurrence of confirmed four-component major adverse cardiovascular events (MACE-4; cardiovascular death, myocardial infarction, stroke and hospitalized unstable angina) between pooled tirzepatide groups and control groups. A stratified Cox proportional hazards model, with treatment as a fixed effect and trial-level cardiovascular risk as the stratification factor, was used for the estimation of hazard ratios (HRs) and confidence intervals (CIs) comparing tirzepatide to control. Data from 4,887 participants treated with tirzepatide and 2,328 control participants were analyzed. Overall, 142 participants, 109 from the trial with high cardiovascular risk and 33 from the six trials with lower cardiovascular risk, had at least one MACE-4 event. The HRs comparing tirzepatide versus controls were 0.80 (95% CI, 0.57–1.11) for MACE-4; 0.90 (95% CI, 0.50–1.61) for cardiovascular death; and 0.80 (95% CI, 0.51–1.25) for all-cause death. No evidence of effect modifications was observed for any subgroups, although the evidence was stronger for participants with high cardiovascular risk. Tirzepatide did not increase the risk of major cardiovascular events in participants with T2D versus controls.

DOI: 10.1038/s41591-022-01707-4

Source: https://www.nature.com/articles/s41591-022-01707-4

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
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