GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS IN PEDIATRIC OBESITY: A SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED TRIALS

Abstract

Background: Pediatric obesity is a complex, multifactorial chronic disease with limited response to lifestyle interventions alone, wherein glucagon-like peptide-1 receptor agonists (GLP-1RA) represent an impactful pharmacological advancement. This systematic review aims to synthesize evidence from randomized controlled trials (RCTs) regarding the weight-loss efficacy and safety of GLP-1RA in children and adolescents with obesity, excluding type 2 diabetes.Methods: Systematic review conducted in adherence to the PRISMA 2020 guidelines. Study selection (screening and full-text appraisal) and data extraction were conducted independently by two reviewers. The search covered PubMed/MEDLINE, Scopus, and LILACS databases (January 2015 to October 2026). Double-blind RCTs evaluating GLP-1RA versus placebo in pediatric subjects aged 6 to < 18 years with obesity were included. Risk of bias was appraised independently using the RoB 2 tool. Certainty of evidence was assessed outcome-by-outcome using the GRADE system. Given the small number and clinical heterogeneity of eligible trials, outcomes were synthesized through a structured narrative synthesis following the SWiM guidelines.Results: A total of 903 records were identified across databases (PubMed: 314, Scopus: 300, LILACS: 289). After removing 589 duplicates, 314 records were screened by title and abstract, with 258 excluded. Full-text review was performed on 56 reports, of which 51 were excluded with documented reasons, leaving 5 RCTs included. Liraglutide 3.0 mg/day significantly reduced BMI z-score by −0.22 (95% CI: −0.37 to −0.08; p = 0.002) and relative BMI by −4.64 percentage points (p.p.) over 56 weeks in adolescents. Once-weekly semaglutide 2.4 mg induced a placebo-subtracted BMI change of −16.7 p.p. (95% CI: −20.3 to −13.2; p < 0.001) at week 68, with 73% achieving ≥ 5% weight reduction. Exenatide XR showed a modest effect, without statistical significance in the intention-to-treat analysis (−4.1%; 95% CI: −8.6 to 0.5), with benefit only in the per-protocol analysis. Transient gastrointestinal adverse events predominated across molecules. Weight regain was observed following treatment cessation. Certainty of evidence (GRADE) was moderate for anthropometric efficacy outcomes and overall tolerability, and low for biliary adverse events and weight regain.Conclusion: GLP-1RA demonstrate consistent efficacy in pediatric obesity management, with semaglutide exhibiting superior weight reduction. The observed weight rebound after withdrawal underscores obesity as a chronic condition requiring sustained therapeutic strategies and vigilant monitoring of biliary events.