Childhood obesity and youth-onset type 2 diabetes mellitus (T2DM) are increasing, highlighting the need for effective treatments beyond lifestyle intervention and metformin. This review systematically evaluated the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in children and adolescents with obesity or T2DM. PubMed-indexed studies published from 2000 to 2025 were reviewed, including seven pivotal randomized controlled trials and six meta-analyses involving 901 participants aged 6 to < 18 years. Semaglutide 2.4 mg/week produced the greatest BMI reduction in adolescents with obesity, followed by liraglutide 3.0 mg/day, which also improved BMI SDS in adolescents and younger children. In youth-onset T2DM, liraglutide 1.8 mg/day and dulaglutide significantly improved HbA1c compared with placebo. Weight-reducing agents also improved insulin resistance and modestly reduced triglycerides, while LDL-cholesterol changes were minimal. Gastrointestinal adverse events, mainly nausea and vomiting, were the most frequent and were generally transient and dose dependent. No significant adverse effects on linear growth or pubertal progression were reported. GLP-1 RAs are effective adjuncts for pediatric obesity and T2DM, but longer-term studies are needed to assess cardiovascular safety, bone health, and growth outcomes.
