GLP-1 Agonists in Adolescent Obesity: A Narrative Review of Single, Dual, and Triple Agonists

Adolescent obesity is an escalating global health concern associated with increased risks of cardiovascular disease, type 2 diabetes mellitus, and long-term metabolic complications. Although lifestyle interventions remain first-line therapy, their limited long-term effectiveness has led to increasing interest in pharmacological approaches. This narrative review evaluates the mechanisms, clinical efficacy, and safety of glucagon-like peptie-1 (GLP-1) receptor agonists, as well as emerging dual and triple incretin-based therapies, in the management of adolescent obesity. A literature search was conducted using PubMed and Scopus, focusing on clinical trials, systematic reviews, and real-world studies published between 2010 and 2024. Evidence from pediatric and adolescent populations was prioritized, while adult data were included where adolescent-specific evidence remains unavailable and are interpreted cautiously. Among single-agent therapies, GLP-1 receptor agonists have demonstrated clinically meaningful weight reduction and metabolic benefits in adolescents. In the STEP TEENS trial, once-weekly semaglutide resulted in approximately 16% mean body weight reduction over 68 weeks, while liraglutide produced more modest reductions. Dual agonists such as tirzepatide and emerging triple agonists, including retatrutide, have shown superior weight-loss efficacy in adult populations; however, pediatric data for these agents remain limited or unavailable. Across all incretin-based therapies, gastrointestinal adverse effects are the most commonly reported side effects. In conclusion, GLP-1 receptor agonists represent an effective pharmacological option for adolescents with obesity, while dual and triple incretin agonists offer promising future therapeutic potential. Nevertheless, the clinical application of multi-receptor agonists in adolescents requires caution, as long-term safety, developmental outcomes, and real-world adherence data in pediatric populations are still lacking. Further well-designed pediatric trials are essential before broader adoption can be recommended.