ESPE Yearbook of Paediatric Endocrinology

N Engl J Med. 2025 Feb 6;392(6):555-565. PMID: 39258838. doi: 10.1056/NEJMoa2407379. https://pubmed.ncbi.nlm.nih.gov/39258838/

Brief Summary: This phase 3 trial demonstrated that in children aged 6 to under 12 years with obesity, 56 weeks of liraglutide (target dose: 3.0 mg/d) combined with lifestyle intervention reduced BMI compared to placebo plus lifestyle changes.

The GLP-1 receptor agonists liraglutide and semaglutide are currently approved for long-term weight management in adolescents aged ≥12 years with obesity, in combination with lifestyle modifications. Their mechanisms involve enhancing satiety, reducing appetite and caloric intake, and dampening food reward, as well as promoting postprandial insulin secretion, suppressing glucagon, and delaying gastric emptying. However, no pharmacological treatments have been approved for non-monogenic, non-syndromic obesity in children under 12 years of age.

This study thus marks a major milestone and will likely pave the way for extending liraglutide approval to children as young as 6 years. Notably, although caution is needed when comparing across different age groups and study designs, the observed greater BMI reduction in younger children here (vs effects in adolescents from previous studies) suggests possible advantages of earlier intervention [1].

These findings support the hypothesis that younger children may respond more favourably to obesity interventions, as also indicated in lifestyle-based studies [2,3]. Introducing pharmacologic therapy at a younger age could potentially alter disease trajectory and prevent the entrenchment of obesity-related metabolic and psychosocial comorbidities. Future long-term data will be crucial to confirm durability, safety, and impacts on quality of life.

References: 1. Kelly AS, Auerbach P, Barrientos-Perez M, et al. A randomized, controlled trial of liraglutide for adolescents with obesity. N Engl J Med 2020; 382: 2117-28.2. Danielsson P, Kowalski J, Ekblom Ö, Marcus C. Response of severely obese children and adolescents to behavioral treatment. Arch PediatrAdolesc Med 2012; 166: 1103-8.3. Prinz N, Pomares-Millan H, Dannemann A, Giordano GN, Joisten C, Körner A, Weghuber D, Weihrauch-Blüher S, Wiegand S, Holl RW, Lanzinger S; APV initiative and the Stratification of Obesity Phenotypes to Optimize Future Therapy (SOPHIA) consortium. Who benefits most from outpatient lifestyle intervention? An IMI-SOPHIA study on pediatric individuals living with overweight and obesity. Obesity (Silver Spring). 2023 Sep;31(9):2375-2385.