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

J Pediatr. 2021 Sep:236:137-147.e13. doi: 10.1016/j.jpeds.2021.05.009. Epub 2021 May 11.

Abstract

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.

Keywords: GLP-1; incretin; pediatric obesity.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adolescent
  • Blood Glucose
  • Blood Pressure
  • Body Mass Index
  • Child
  • Glucagon-Like Peptide-1 Receptor / therapeutic use*
  • Glycated Hemoglobin
  • Humans
  • Pediatric Obesity / drug therapy*
  • Pediatric Obesity / metabolism
  • Pediatric Obesity / physiopathology

Substances

  • Blood Glucose
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A