胰高血糖素样肽1受体激动剂治疗儿童和青少年肥胖的有效性和安全性Meta分析

Efficacy and safety of glucagon-like peptide-1 receptor agonists in children and adolescents with obesity:A systematic review and meta-analysis

背景越来越多的研究表明,胰高血糖素样肽1(GLP-1)受体激动剂除了具有显著的降糖作用外,还具有减重作用,对仍处于生长发育期的儿童和青少年,GLP-1受体激动剂的反应和耐受性不同于成人,长期的有效性和安全性目前仍不明确。目的采用系统评价/Meta分析方法评价GLP-1受体激动剂治疗儿童和青少年肥胖的疗效和安全性。设计系统评价/Meta分析。方法检索PubMed、Cochrane Library、Embase、Web of Science、中国知网、万方及维普数据库,检索时间为2005年4月1日至2021年8月1日,收集和评估GLP-1受体激动剂治疗儿童和青少年肥胖的RCT文献,依照纳入和排除标准进行文献筛选和数据提取后,运用Revman 5.3软件进行Meta分析。主要结局指标GLP-1受体激动剂治疗儿童和青少年肥胖的疗效和安全性。结果9篇RCT文献进入Meta分析,2篇为交叉RCT,7篇为平行RCT;共纳入了565例儿童及青少年肥胖患儿,试验组293例(利拉鲁肽235例,艾塞那肽58例),安慰剂组272例;年龄7~19岁,研究周期5~56周。文献偏倚风险中等。Meta分析结果提示,与安慰剂组相比,GLP-1受体激动剂可降低儿童和青少年肥胖患儿的BMI(MD=-1.46 kg·m^(-2),95%CI:-1.93~-0.98,P<0.05)、体重(MD=-2.29 kg,95%CI:-3.68~-0.90,P<0.05)、腰围(MD=-2.42 cm,95%CI:-4.36~-0.47,P<0.05)、伴糖尿病者糖化血红蛋白(MD=-0.91%,95%CI:-1.05~-0.77,P<0.05),但会升高低血糖(OR=2.00,95%CI:1.20~3.34,P<0.05)、恶心(OR=3.83,95%CI:2.43~6.04,P<0.05)和呕吐(OR=4.32,95%CI:1.87~10.02,P<0.05)等胃肠道不良反应的发生率。结论在生活方式干预的基础上给予GLP-1受体激动剂可降低儿童和青少年肥胖患儿的体重和BMI值,但使轻度胃肠道不良反应和低血糖的发生率增加。

Background A great number of studies have shown that glucagon-like peptide-1(GLP-1)receptor agonists not only exert significant hypoglycemic effects,but also have important effects on losing weight.For the special group of children and adolescents who are still in the growth and development stage,the response and tolerability of GLP-1 receptor agonists are different from those of adults,and the long-term efficacy and safety are still not very clear.Objective To systematically review and meta-analyse the efficacy and safety of GLP-1 agonists in children and adolescents with obesity.Design System review/Meta analysis.Methods PubMed,Cochrane,Embase,Web of Science,CNKI,Wanfang and VIP database were searched to collect the randomized controlled trial(RCT)evaluating the effects of glucagon-like peptide-1 receptor agonists on children and adolescents with obesity from April 1,2005 to August 1,2021.After literature screening and data extraction,the meta-analysis was performed by RevMan 5.3 software.Main outcome measures The efficacy and safety of GLP-1 agonists in children and adolescents with obesity.Results A total of 9 RCTs were included in the meta-analysis with 2 cross-over randomized controlled trials and 7 parallel randomized controlled trials.A total of 565 children and adolescents with obesity were enrolled,including 293 cases in the experimental group(235 cases of liraglutide and 58 cases of exenatide)and 272 cases in the placebo group.They were between 7 and 19 years old,and the study period was 5 to 56 weeks.The risk of literature bias was low to moderate.Pooled analysis suggested that GLP-1 receptor agonists were superior to placebo with regard to the change from baseline in the BMI(MD=-1.46 kg·m^(-2),95%CI:-1.93--0.98,P<0.05),body weight(MD=-2.29 kg,95%CI:-3.68--0.90,P<0.05),waist circumference(MD=-2.42 cm,95%CI:-4.36--0.47,P<0.05)and glycated hemoglobin(MD=-0.91%,95%CI:-1.05--0.77,P<0.05).Compared to placebo,more participants in GLP-1 receptor agonists groups had hypoglycemia(OR=2.00,95%CI:1.20-3.34,P<0.05)and gastrointestinal symptoms including nausea(OR=3.83,95%CI:2.43-6.04,P<0.05)and vomiting(OR=4.32,95%CI:1.87-10.02,P<0.05).Conclusion For children and adolescents with obesity,the use of GLP-1 receptor agonists based on lifestyle modification can significantly reduce the body weight and BMI.But at the same time,there is also a higher proportion of gastrointestinal side effects and the incidence of hypoglycemia.