Pharmacotherapy for Children and Adolescents With Overweight or Obesity: A Systematic Review and Network Meta‐Analysis of Randomized Controlled Trials

AIMS: The escalating global prevalence of childhood and adolescent overweight and obesity constitutes a pressing public health issue. This network meta-analysis aimed to compare the efficacy and safety of pharmacologic interventions as adjuncts to lifestyle therapy in this population. MATERIALS AND METHODS: Randomized controlled trials (RCTs) were sourced from systematic searches of PubMed, Embase (using the OVID platform), the Cochrane Library (CENTRAL), the WHO International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov from database inception to July 28, 2025. A frequentist network meta-analysis was performed using a random-effects model. We used the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach to evaluate the overall certainty of evidence and categorized the interventions. RESULTS: A total of 41 RCTs (N = 3923) were included. Compared with lifestyle modification alone, semaglutide produced the largest reduction in the 95th BMI percentile (MD -20.40%, 95% CI -24.22 to -16.58), with an additional 500 and 399 patients per 1000 person-years achieving ≥ 5% and ≥ 10% BMI reduction, respectively. Phentermine-topiramate showed the next largest reduction (MD -18.35%, 95% CI -22.26 to -14.45), corresponding to 554 and 734 additional responders per 1000 person-years. Liraglutide and exenatide also significantly reduced the 95th BMI percentile compared with lifestyle modification alone, although the reductions were smaller than those achieved with semaglutide and phentermine-topiramate. CONCLUSIONS: Both semaglutide and phentermine-topiramate were closely linked to weight management, and phentermine-topiramate, with its favourable tolerability, may serve as the optimal adjunct to lifestyle interventions.