目的 胰高血糖素样肽-1（GLP-1）受体激动剂是有效的降糖药物。临床试验研究证实了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。本研究采用系统评价/Meta分析来评价胰高血糖素样肽-1受体激动剂对2型糖尿病患者心血管结局的影响。方法 计算机检索中国生物医学文献数据库（CBM）、中国学术期刊全文数据库/中国知网（CNKI）、万方数据库、PubMed、Web ofScience、EMbase和Cochrane Library数据库，检索日期自建库至2021年6月30日。纳入所有符合检索策略且提供了GLP-1受体激动剂与安慰剂的治疗结局的随机对照试验（RCT），使用固定/随机效应模型分析主要结局指标主要不良心血管事件（MACE，包括但不限于心血管死亡率、非致命性心肌梗死和非致命性卒中）及严重不良事件的发生情况。利用RevMan 5.3软件进行Meta分析。结果 最终纳入7个RCT研究，共计56 004例2型糖尿病患者。在我们搜索和筛选的文章中，确定了6种GLP-1受体激动剂：杜拉鲁肽、利拉鲁肽、塞马鲁肽、艾塞那肽、利西塞那肽和阿比鲁肽。与安慰剂相比，GLP-1受体激动剂治疗在MACE方面的相对风险降低11%（RR=0.89，95%CI：0.85~0.94，P＜0.00001）。其中心血管死亡率风险降低11%（95%CI：0.82~0.96，P=0.002），致命或非致命性心肌梗死和卒中的风险分别降低7%（95%CI：0.87~0.99，P=0.03）和15%（95%CI：0.77~0.93，P=0.0009），全因死亡率相对风险降低16%（95%CI：0.76~0.94，P=0.001），因心力衰竭住院的风险降低9%（95%CI：0.84~1.00，P=0.04），且肾脏疾病新发或加重的相对风险降低18%（95%CI：0.76~0.89，P＜0.00001）。GLP-1受体激动剂对不稳定型心绞痛住院的风险无显著影响。GLP-1受体激动剂和安慰剂在视网膜病变、严重低血糖、急性胰腺炎、胰腺癌或甲状腺癌的发生风险上无显著性差异。结论 所有GLP-1受体激动剂的心血管安全性较高，此类药物可降低主要不良心血管事件、全因死亡率和心力衰竭住院的风险，且不增加严重并发症的风险，应根据患者需求进行个性化药物选择。

Objective To review the influence of glucagon-like peptide-1 (GLP-1) receptor agonists on cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) by applying a Meta-analysis. Methods The databases of CBM, CNKI, WanFang Data, PubMed, Web of Science, EMbase and Cochrane Library were retrieved with computer from database establishment time to June 30, 2021. All randomized controlled trials (RCT) were included, which were eligible for retrieving strategies and provided therapeutic outcomes of GLP-1 receptor agonists and placebo. The primary outcome indexes of major adverse cardiovascular events (MACE, including, but not limited to, mortality due to cardiovascular diseases, non-fatal myocardial infarction and non-fatal stroke) and incidence of severe adverse events were analyzed by using fixed-effect model or random-effects model. A Metaanalysis was conducted by using RevMan 5.3 software. Results There were finally 7 RCT included involved in 56004 patients with T2DM. In all retrieved and screened articles, there were 6 GLP-1 receptor agonists determined including dulaglutide, liraglutide, semaglutide, exenatide, lixisenatide and albiglutide. In GLP-1 receptor agonist treatment, the relative MACE risks were reduced by 11% (RR=0.89, 95%CI: 0.85~0.94, P<0.00001) compared with placebo, among which the risk of mortality due to cardiovascular diseases was reduced by 11% (95%CI: 0.82~0.96, P=0.002), risk of fatal or non-fatal myocardial infarction was reduced by 7% (95%CI: 0.87~0.99, P=0.03), risk of stroke was reduced by 15% (95%CI: 0.77~0.93, P=0.0009), relative risk of all-cause mortality was reduced by 16% (95%CI: 0.76~0.94, P=0.001), risk of hospitalization due to heart failure was reduced by 9%(95%CI: 0.84~1.00,P=0.04), and relative risks of new-onset or exacerbated kidney diseases were reduced by 18% (95%CI: 0.76~0.89, P<0.00001). GLP-1 receptor agonists had no significant affect on risk of hospitalization due to unstable angina pectoris (UAP). GLP-1 receptor agonists and placebo had no significant difference in the risks of retinopathy, severe hypoglycemia, acute pancreatitis, pancreatic cancer or thyroid cancer. Conclusion All GLP-1 receptor agonists have higher safety for cardiovascular diseases, and they can reduce the risks of MACE, all-cause mortality and hospitalization due to heart failure without improving the risks of severe complications. The choice of GLP-1 receptor agonists should be allowed to be individualized to each patient’s needs.

天津市卫健委激素与发育重点实验室 天津市代谢性疾病重点实验室项目(ZXY-ZDSYS2020-8)