Abstract: 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.

Key words: Glucagon-like peptide-1 receptor agonists, Obesity, Children, Adolescents, Meta-analysis