Glucagon-like peptide-1 receptor agonists (GLP-1s), including semaglutide and liraglutide, are effective pharmacologic options for pediatric obesity, producing significant weight loss, cardiometabolic improvements, and reductions in barriers to physical activity. By alleviating pain, mechanical load, and psychosocial burden, these agents can also create a window to initiate sustainable health behaviors in adolescents. However, use during critical developmental periods raises concerns regarding long-term effects on musculoskeletal maturation. Adolescence is marked by rapid accrual of muscle and bone mass, and GLP-1-associated weight loss may attenuate this process, potentially reducing peak musculoskeletal capacity and increasing future frailty risk. This perspective piece advocates for integration of tailored exercise prescription with GLP-1 medication therapy. Given limited longitudinal pediatric data, a balanced approach is necessary. GLP-1s should be integrated within a multimodal framework emphasizing resistance training, weight-bearing activity, and optimized nutrition particularly adequate protein intake to preserve lean mass. Exercise may also synergize with GLP-1-mediated metabolic improvements to enhance functional outcomes. Clinicians should provide individualized, developmentally appropriate guidance that addresses access barriers and patient preferences while reinforcing that pharmacotherapy is not a substitute for lifestyle intervention. Integrated care models that prioritize musculoskeletal integrity and functional health are essential to maximizing long-term outcomes, underscoring the need for longitudinal research in pediatric populations.
