Beyond Weight Loss: Optimizing GLP-1 Receptor Agonist Use in Children

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a transformative therapy for obesity and type 2 diabetes (T2D) in pediatric populations. This review synthesizes current evidence on efficacy, safety, and knowledge gaps in children and adolescents. Methods: A structured review of randomized controlled trials, extension studies, and mechanistic investigations evaluating GLP-1RAs in pediatric obesity and T2D was conducted. Outcomes of interest included body weight, BMI, body composition, glycemic control, and adverse events. Results: In adolescents, liraglutide and semaglutide consistently produce clinically meaningful reductions in BMI, body weight, and waist circumference, with modest improvements in systolic blood pressure and minimal effects on lipid levels or HbA1c. A newer trial in children 6 to <12 years showed liraglutide reduced BMI compared with placebo, with GI events consistent with prior safety profiles. Weight loss tends to include both fat and lean components; rapid weight loss may impair muscle strength or bone density if resistance exercise and adequate protein intake are not ensured. Risks include micronutrient gaps, misuse, and uncertain long-term effects on growth and puberty. These important considerations remain largely unaddressed in pediatric studies, and adult data can't be directly extrapolated to children due to developmental, hormonal, and physiological differences. Conclusions: GLP-1 RAs are a promising adjunct to lifestyle therapy for pediatric obesity, but pediatric-specific protocols are needed to safeguard musculoskeletal health, ensure nutritional adequacy, and minimize misuse. Critical gaps remain in pediatric pharmacokinetics, dosing strategies, and long-term developmental safety. Further research is essential to develop evidence-based guidelines for safe and effective pediatric anti-obesity therapy.