Safety and Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Children and Adolescents with Obesity: A Meta-Analysis

Objectives: To determine the weight, body mass index (BMI), cardiometabolic, and gastrointestinal effects of glucagon-like peptide-1 (GLP-1) receptor agonists in children with obesity. Study design: Web of Science, PubMed/MEDLINE, and Scopus databases from 01/01/1994-01/01/2021 for randomized control trials examining the weight, BMI, cardiometabolic, or gastrointestinal effects of GLP-1 receptor agonists in children and adolescents with obesity. Data were extracted by 2 independent surveyors and a random effects model was applied to meta-analyze generic inverse variance outcomes. Primary outcomes were related to weight and cardiometabolic profile, and secondary outcomes of interest were gastrointestinal-related treatment-emergent adverse events. Results: Nine studies involving 574 participants were identified, of which 3 involved exenatide and 6 involved liraglutide. GLP-1 receptor agonists use caused a modest reduction in body weight (mean difference [MD] -1.50 [-2.50,-0.50] kg, I² 64%), BMI (MD -1.24 [-1.71,-0.77] kg/m², I² 0%), and BMI z score (MD -0.14 [-0.23,-0.06], I² 43%). Glycemic control was improved in children with proven insulin resistance (glycated hemoglobin A1c MD -1.05 [-1.93,-0.18] %, I² 76%). Although no lipid profile improvements were noted, a modest decrease in systolic blood pressure was detected (MD -2.30 [-4.11,-0.49] mm Hg; I² 0%). Finally, analysis of gastrointestinal-related treatment-emergent adverse events revealed an increased risk of nausea (risk ratio 2.11 [1.44, 3.09]; I² 0%), without significant increases in other gastrointestinal symptoms. Conclusions: This meta-analysis indicates that GLP-1 receptor agonists are safe and effective in modestly reducing weight, BMI, glycated hemoglobin A1c, and systolic blood pressure in children and adolescents with obesity in a clinical setting, albeit with increased rates of nausea. PROSPERO ID: CRD42020195869.