Pharmacological Management of Obesity in the Pediatric Population

Abstract

Pediatric obesity is a chronic, multifactorial disease affecting approximately 160 million children worldwide, driven by complex interactions between genetic, neuroendocrine, environmental, and behavioral factors. Lifestyle modification remains the first-line treatment, but evidence consistently shows it produces only modest, unsustained BMI reductions in moderate-to-severe cases. Pharmacological agents are increasingly recommended as adjuncts, particularly for adolescents aged 12 and older who respond inadequately to lifestyle therapy alone. GLP-1 receptor agonists, especially semaglutide, have emerged as the most efficacious agents, with the STEP TEENS trial demonstrating a 16.1% BMI reduction versus placebo, while orlistat and metformin offer more modest and inconsistent benefits. Emerging precision therapies such as setmelanotide target specific genetic pathways, representing a shift from generalized weight-loss approaches toward mechanism-based, individualized treatment. Key limitations remain, including scarce long-term safety data, post-discontinuation weight regain, limited evidence in children under 12, and inequitable access to newer agents across healthcare settings.