Metabolic outcomes and safety of GLP-1 receptor agonists in children and adolescents with obesity: A systematic review and meta-analysis.

Background: Glucagon-like peptide 1 receptor agonists have been proven to be effective in adults with obesity. However, robust evidence on their effects on body weight, obesity-related metabolic changes, and safety in children and adolescents with obesity remains limited, making them a subpopulation with scant treatment options. Therefore, this meta-analysis aimed to determine more precise estimates of the efficacy and safety of glucagon-like peptide-1 agonists in pediatric obesity.

Methods: Three databases were searched (PubMed, Embase, and Cochrane Central Register of Controlled Trials) for trials published until the half of September 2024. The search indexing terms included 3 categories: [1] obesity [2], youth, and [3] glucagon-like peptide-1 receptor agonist (GLP-1 RA). Randomized controlled trials in youth with obesity (age ≤ 18 years) that assessed anthropometric and metabolic parameters were included. A total of 2016 studies were retrieved, and 24 full-text articles were screened. The data were analyzed using both mean differences (MDs) and standardized mean differences (SMDs) with 95% CIs and odds ratios (ORs) with 95% CIs. We applied a random effects model. Our outcomes were body weight (BW), BMI, waist circumference (WC), lipid profile, Hb1Ac, fasting blood glucose (FBG), blood pressure, and side effects.

Results: Eight studies comprised of 715 children and adolescents were included. On average, GLP-1 RA reduced BMI (SMD -0.67; 95% CI -0.8 to -0.41), BW (SMD -0.60; 95% CI -0.89 to -0.44), and WC (SMD -0.40; 95% CI -0.61 to -0.18). Although lipid profiles, HbA1c, and FBG were unaffected, GLP-1 RA was linked to a slight reduction in SBP (SMD -0.20; 95% CI -0.35 to -0.04) and an increase in HR (SMD + 0.26; 95% CI + 0.07 to +0.46), with no significant effect on DBP. Adverse effects, primarily nausea and vomiting, were more common in the intervention group, although trial withdrawal rates remained low.

Conclusions: Within this specific population, GLP-1 RAs exhibit significant reductions in BW, BMI, WC, and SBP. The analyses of lipid profiles, DBP, HbA1c, and FBG showed no significant changes. Also, the administration of these medications is concurrent with an elevated incidence of side effects, which are predominantly gastrointestinal and tolerable.

Trial Registration: PROSPERO identifier: CRD42024532845.