GLP-1 receptor agonists in adolescent obesity: Incretin-based therapies during a sensitive developmental period

Adolescent obesity is a chronic disease associated with early cardiometabolic dysfunction and long-term health risk. Behavioral interventions alone produce modest and unsustained weight loss, leading to increasing use of pharmacotherapy. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as highly effective treatments for obesity, producing clinically significant reductions in body weight and improvements in glycemic control. Short-term safety profiles are characterized primarily by transient gastrointestinal symptoms and low rates of serious adverse events or psychiatric symptoms. However, the developmental implications and long-term effects have yet to be evaluated. The purpose of this review is to summarize existing literature concerning the use of GLP-1RAs for adolescents with obesity and to discuss the implications of GLP-1RA use in the adolescent population. This review serves to both identify areas of potential concern and to highlight the need for continued research. Although GLP-1RAs demonstrate robust efficacy for the treatment of adolescent obesity, adolescence is a sensitive period of development and critical knowledge gaps remain regarding long-term effects of GLP-1RAs on growth, pubertal development, cognition, neural reward processing, and lifelong energy balance regulation. Longitudinal and mechanistic studies are needed to determine the long-term effects on development and to guide safe, developmentally informed clinical use.