Monami M, Dicembrini I, Nardini C, Fiordelli I, Mannucci E
Geriatric Cardiology, Careggi Teaching Hospital, Florence, Italy.
Diabetes Obes Metab. 2014 Jan;16(1):38-47. doi: 10.1111/dom.12175. Epub 2013 Jul 28.
New drugs for type 2 diabetes need to demonstrate their cardiovascular safety, due regulatory requirements from the Food and Drug Administration. For this reason, glucagon-like peptide-1 receptor agonists (GLP-1 RA) are currently undergoing large-scale, long-term randomized trials specifically designed for cardiovascular outcomes. Aim of the present meta-analysis of randomized clinical trials is the assessment of the effects of GLP-1 RA on major cardiovascular events (MACE), mortality and cardiovascular risk factors.
A meta-analysis was performed including all trials with a duration of at least 6 months, comparing a GLP-1 RA with a non-GLP-1 RA agent in type 2 diabetes. MACE and mortality were retrieved and combined to calculate Mantel-Haenzel odds ratio (MH-OR). Furthermore, data on endpoint systolic and diastolic blood pressure, total and high-density lipoprotein (HDL) cholesterol and triglyceride were collected.
Of 37 selected trials, 33 reported information on MACE, and 25 reported at least one event. The difference in the incidence of MACE between GLP-1 RA and comparators did not reach statistical significance [MH-OR 0.78 (0.54-1.13), p = 0.18]. GLP-1 RA were associated with a significant reduction in the incidence of MACE in comparisons with placebo and pioglitazone, with a non-significant trend towards reduction in DPP4i-controlled studies. No significant effect of GLP-1 RA was observed on mortality, although a non-significant favourable trend was observed in comparisons with placebo.
The present meta-analysis confirms the cardiovascular safety of GLP-1 RA, at least in the short term and in low-risk individuals. GLP-1 RA could have a beneficial effect on the incidence of MACE, at least in comparison with placebo.
由于美国食品药品监督管理局的监管要求，2型糖尿病新药需要证明其心血管安全性。因此，胰高血糖素样肽-1受体激动剂（GLP-1 RA）目前正在进行专门针对心血管结局设计的大规模、长期随机试验。本随机临床试验的荟萃分析目的是评估GLP-1 RA对主要心血管事件（MACE）、死亡率和心血管危险因素的影响。
进行一项荟萃分析，纳入所有持续时间至少6个月的试验，比较2型糖尿病中GLP-1 RA与非GLP-1 RA药物。检索并合并MACE和死亡率以计算Mantel-Haenzel优势比（MH-OR）。此外，收集关于终点收缩压和舒张压、总胆固醇和高密度脂蛋白（HDL）胆固醇以及甘油三酯的数据。
在37项入选试验中，33项报告了MACE信息，25项报告了至少1起事件。GLP-1 RA与对照药物之间MACE发生率的差异未达到统计学显著性[MH-OR 0.78（0.54 - 1.13），p = 0.18]。与安慰剂和吡格列酮相比，GLP-1 RA与MACE发生率的显著降低相关，在DPP4i对照研究中有降低趋势但不显著。未观察到GLP-1 RA对死亡率有显著影响，尽管与安慰剂相比有不显著的有利趋势。
本荟萃分析证实了GLP-1 RA的心血管安全性，至少在短期内和低风险个体中如此。GLP-1 RA可能对MACE发生率有有益影响，至少与安慰剂相比是这样。
