胰高血糖素样肽-1受体激动剂治疗儿童及青少年肥胖的疗效与安全性的系统评价  

Systematic Review on Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Obesity in Children and Adolescents

作　　者：杨春松[1,2] 舒安琴 吴瑾 张伶俐[1,2] YANG Chunsong;SHU Anqin;WU Jin;ZHANG Lingli(Dept.of Pharmacy/Evidence Based Pharmacy Center,West China Second Hospital,Sichuan University,Chengdu 610041,China;Key Laboratory of Birth Defects and Related Maternal and Child Diseases,Ministry of Education,Chengdu 610041,China;Cancer Hospital Affiliated to Chongqing University,Chongqing 400030,China;Dept.of Pediatrics,West China Second Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西第二医院药学部/循证药学中心,成都610041 [2]出生缺陷与相关妇儿疾病教育部重点实验室,成都610041 [3]重庆大学附属肿瘤医院,重庆400030 [4]四川大学华西第二医院儿科,成都610041

出　　处：《中国医院用药评价与分析》2024年第9期1127-1131,1135,共6页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：中华国际医学交流基金会项目(No.Z-2017-26-1902-5)。

摘　　要：目的:系统评价胰高血糖素样肽-1(GLP-1)受体激动剂治疗儿童及青少年肥胖的疗效与安全性。方法:计算机检索PubMed、Embase、Web of Science、the Cochrane Library、中国知网、万方数据库、维普数据库中关于GLP-1受体激动剂对比安慰剂治疗儿童及青少年肥胖的随机对照试验(RCT)文献(数据库建库至2023年12月31日),根据纳入与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。结果:共纳入11篇RCT文献,涉及981例儿童及青少年肥胖患者,其中研究组542例(利拉鲁肽227例,艾塞那肽78例,司美格鲁肽134例,度拉糖肽103例),对照组439例。文献偏倚风险中等。Meta分析结果显示,与安慰剂相比,GLP-1受体激动剂可降低儿童及青少年肥胖患者的体重(MD=-3.83,95%CI=-5.94~-1.71,P=0.000 4)、体重指数(BMI)(MD=-1.94,95%CI=-3.17~-0.70,P=0.002)、BMI-Z评分(MD=-0.18,95%CI=-0.33~-0.03,P=0.02)、糖化血红蛋白水平(MD=-0.22,95%CI=-0.38~-0.07,P=0.005)、空腹血糖水平(MD=-4.43,95%CI=-8.18~-0.68,P=0.02),差异均有统计学意义。亚组分析结果显示,周制剂在降低患者体重方面可能不具有优势,但周制剂相比于日制剂能更好地降低患者的BMI、BMI-Z评分;同时,相比于不伴有2型糖尿病的儿童及青少年肥胖患者,GLP-1受体激动剂可以更好地降低伴有2型糖尿病的儿童及青少年肥胖患者的空腹血糖和糖化血红蛋白水平。相对于安慰剂,使用GLP-1受体激动剂的儿童及青少年肥胖患者的恶心(OR=3.13,95%CI=2.23~4.39,P<0.000 01)、呕吐(OR=5.97,95%CI=3.79~9.41,P<0.000 01)、腹泻(OR=1.45,95%CI=1.02~2.06,P=0.04)、头晕(OR=2.68,95%CI=1.36~5.26,P=0.004)等不良反应发生率升高,差异均有统计学意义。结论:GLP-1受体激动剂可降低儿童及青少年肥胖患者的体重、BMI、糖化血红蛋白、空腹血糖水平,但胃肠道不良反应发生率较高,使用时应注意。OBJECTIVE:To systematically review the efficacy and safety of glucagon-like peptide-1(GLP-1)receptor agonists in the treatment of obesity in children and adolescents.METHODS:PubMed,Embase,Web of Science,the Cochrane Library,CNKI,Wanfang Data,and VIP databases were retrieved from 2000 to 2023 for randomized controlled trials(RCT)of GLP-1 receptor agonists and placebo in the treatment of obesity in children and adolescents(from database establishment to Dec.31st,2023).Literature screening and data extraction were performed based on inclusion and exclusion criteria,and Meta-analysis was performed using RevMan 5.3 software.RESULTS:A total of 11 RCT were enrolled,including 981 children and adolescents with obesity.There were 542 cases in the study group(227 cases of liraglutide,78 cases of exenatide,134 cases of semaglutide,103 cases of duraglutide)and 439 cases in the control group.The risk of literature bias was moderate.Meta-analysis results showed that compared with the placebo,GLP-1 receptor agonists can reduce body mass(MD=-3.83,95%CI=-5.94--1.71,P=0.0004),body mass index(BMI)(MD=-1.94,95%CI=-3.17--0.70,P=0.002),BMI-Z score(MD=-0.18,95%CI=-0.33--0.03,P=0.02),glycated hemoglobin(HbA 1c)(MD=-0.22,95%CI=-0.38--0.07,P=0.005),and fasting blood glucose(MD=-4.43,95%CI=-8.18--0.68,P=0.02)in children and adolescents with obesity,with statistically significant differences.Subgroup analysis showed that weekly preparations may not have statistical significance in reducing body mass,yet weekly preparations could better reduce BMI and BMI-Z scores compared with daily preparations.Meanwhile,GLP-1 receptor agonists significantly lower fasting blood glucose and HbA 1c levels in obese children and adolescents with type 2 diabetes compared with those without type 2 diabetes.Compared with the control group,GLP-1 receptor agonists increased the incidence of nausea(OR=3.13,95%CI=2.23-4.39,P<0.00001),vomiting(OR=5.97,95%CI=3.79-9.41,P<0.00001),diarrhea(OR=1.45,95%CI=1.02-2.06,P=0.04),and dizziness(OR=2.68,95%CI=1.36-5.26,P=0.004),with

关 键 词：胰高血糖素样肽-1受体激动剂 儿童 青少年 肥胖 系统评价 

分 类 号：R977.15[医药卫生—药品]