Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis
Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis
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DOI：
10.1016/s2213-8587(17)30412-6
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发表时间：
2018-02-01
影响因子：
44.5
通讯作者：
Holman, Rury R.
中科院分区：
文献类型：
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作者：
Bethel, M. Angelyn;Patel, Rishi A.;Holman, Rury R.
背景胰高血糖素样肽-1（GLP-1）受体激动剂是有效的降糖药物。心血管结局试验的结果显示GLP-1受体激动剂的心血管安全性，但心血管疗效的结果各不相同。我们的目的是检查利司那肽、利拉鲁肽、Semaglutide和缓释艾塞那肽的总体心血管疗效。帕拉;&帕拉;方法在本系统综述和荟萃分析中，我们分析了来自合格试验的数据，这些试验评估了GLP-1受体激动剂与安慰剂相比在成人2型糖尿病患者（18岁或以上）中的安全性和有效性，主要结局包括但不限于心血管死亡率、非致死性心肌梗死和非致死性卒中。我们检索了截至2017年9月18日无语言限制的PubMed和MEDLINE，以获得合格的试验。我们使用随机效应模型对现有的试验数据进行了荟萃分析，以计算心血管疗效结局的总体风险比（HR）和关键安全性结局的比值比。帕拉;&帕拉;结果在我们检索和筛选的12篇文章中，确定了4项GLP-1受体激动剂的心血管结局试验：ELIXA（利司那肽）、LEADER（利拉鲁肽）、SUSTAIN 6（Semaglutide）和EXSCEL（缓释艾塞那肽）。与安慰剂相比，GLP-1受体激动剂治疗显示三点主要不良心血管事件主要结局的相对风险显著降低10%（心血管死亡率、非致死性心肌梗死和非致死性卒中; HR 0.90，95%CI 0.82-0.99; p=0.033），心血管死亡率的RR为13%，（0.87，0.79-0.96; p=0.007），全因死亡率相对风险降低12%（0.88，0.81-0.95; p=0.002），试验间统计异质性为低至中度。未发现GLP-1受体激动剂对致死性和非致死性心肌梗死、致死性和非致死性卒中、因不稳定型心绞痛住院或因心力衰竭住院的显著影响。总体而言，GLP-1受体激动剂治疗和安慰剂治疗之间报告的严重低血糖、胰腺炎、胰腺癌或甲状腺髓样癌没有显著差异。帕拉;&帕拉;我们的研究结果显示，所有GLP-1受体激动剂心血管结局试验均具有心血管安全性，并表明该类药物可降低三点主要心血管不良事件、心血管死亡率和全因死亡风险，尽管单个药物的降低程度不同，但无显著安全性问题。GLP-1受体激动剂总体上具有有利的风险-获益平衡，这应允许根据每例患者的需求个性化选择药物。
Background Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs. Findings from cardiovascular outcome trials showed cardiovascular safety of GLP-1 receptor agonists, but results for cardiovascular efficacy were varied. We aimed to examine overall cardiovascular efficacy for lixisenatide, liraglutide, semaglutide, and extended-release exenatide.& para;& para;Methods In this systematic review and meta-analysis, we analysed data from eligible trials that assessed the safety and efficacy of GLP-1 receptor agonists compared with placebo in adult patients (aged 18 years or older) with type 2 diabetes and had a primary outcome including, but not limited to, cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. We searched PubMed and MEDLINE without language restrictions up to Sept 18, 2017, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (H Rs) for cardiovascular efficacy outcomes and odds ratios for key safety outcomes.& para;& para;Findings Of 12 articles identified in our search and screened for eligibility, four trials of cardiovascular outcomes of GLP-1 receptor agonists were identified: ELIXA (lixisenatide), LEADER (liraglutide), SUSTAIN 6 (semaglutide), and EXSCEL (extended-release exenatide). Compared with placebo, GLP-1 receptor agonist treatment showed a significant 10% relative risk reduction in the three-point major adverse cardiovascular event primary outcome (cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke; HR 0.90,95% CI 0.82-0.99; p=0.033), a 13% RRR in cardiovascular mortality (0.87, 0.79-0.96; p=0.007), and a 12% relative risk reduction in all-cause mortality (0.88, 0.81-0.95; p=0.002), with low-to-moderate between-trial statistical heterogeneity. No significant effect of GLP-1 receptor agonists was identified on fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, hospital admission for unstable angina, or hospital admission for heart failure. Overall, no significant differences were seen in severe hypoglycaemia, pancreatitis, pancreatic cancer, or medullary thyroid cancer reported between GLP-1 receptor agonist treatment and placebo.& para;& para;Interpretation Our findings show cardiovascular safety across all GLP-1 receptor agonist cardiovascular outcome trials and suggest that drugs in this class can reduce three-point major adverse cardiovascular events, cardiovascular mortality, and all-cause mortality risk, albeit to varying degrees for individual drugs, without significant safety concerns. GLP-1 receptor agonists have a favourable risk-benefit balance overall, which should allow the choice of drug to be individualised to each patient's needs.