Pharmacological interventions for the treatment of obesity in children and adolescents.

rationaleTreating obesity in children and adolescents is complex, given the dynamic nature of growth and development during this life stage. The role of pharmacological treatments in the management of pediatric obesity remains uncertain, particularly with respect to outcomes beyond weight reduction, including quality of life and long-term adverse events.

objectivesTo assess the benefits and harms of pharmacological interventions for the treatment of obesity in children and adolescents. SEARCH

methodsWe searched CENTRAL, MEDLINE, the World Health Organization (WHO) International Clinical Trials Registry Platform, and ClinicalTrials.gov on 3 July 2023 without language restrictions. In June 2025, we checked the status of ongoing studies and updated results accordingly. ELIGIBILITY CRITERIA: We included randomized controlled trials (RCTs) evaluating pharmacological interventions in children (0 to 9 years) and adolescents (10 to 19 years) with essential obesity. Eligible studies administered any medication, at any dose, as monotherapy or in combination, for at least three months and reported outcomes after a minimum follow-up of six months. OUTCOMES: Critical outcomes were change in body mass index (BMI), change in weight, any adverse events, discontinuation due to adverse events, and incidence or severity of obesity-related outcomes. Important outcomes were health-related quality of life, mental and physical well-being, and obesity-related disability. RISK OF BIAS: We used the RoB 2 tool to assess bias in the included RCTs. SYNTHESIS

methodsWe calculated mean differences (MDs) and standardized mean differences (SMDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, with their corresponding 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence for critical outcomes and quality of life. INCLUDED STUDIES: We included 37 RCTs with a total of 4218 participants. Two were cross-over trials; 35 were parallel-group trials. We identified seven ongoing studies and six studies as awaiting classification. Of the included studies, 25 involved adolescents only. Eleven studies planned to include both children and adolescents, but only eight actually did. One study intended to include children but did not specify participants' age at inclusion. Trials randomized participants to pharmacological interventions or control alongside common baseline treatments (e.g. behavioral or lifestyle approaches, diet, and physical activity). Of the 37 included studies, 31 used placebo and six used no intervention (baseline treatment alone) as the comparator. The studies were conducted across 17 high-income, six middle-income, and three low-income countries. Length of follow-up ranged from six to 31 months, with a median of 11 months. SYNTHESIS OF

resultsPharmacological interventions versus placebo Compared to placebo, pharmacological interventions (glucagon-like peptide-1 [GLP-1] receptor agonists, metformin, orlistat, sibutramine, topiramate, phentermine plus topiramate) may reduce BMI (change from baseline) by 1.80 kg/m AUTHORS'

conclusionsThis review includes clinical trials assessing the benefits and harms of pharmacological treatments - including GLP-1 agonists, metformin, orlistat, phentermine, sibutramine, and topiramate - for weight management in adolescents with obesity. Evidence suggests that pharmacological treatments may result in small reductions in BMI and weight, which could be clinically important, although effects vary by medication. Evidence on desirable and undesirable effects in children is scant. Uncertainties remain about the optimal duration of treatment, consequences of treatment discontinuation, and long-term benefits and harms, particularly considering the physiology of children and impact on growth. Studies with longer follow-up are needed to evaluate outcomes beyond BMI and weight change, including the potential effects of treatment discontinuation.

fundingThe Department of Nutrition and Food Safety at the WHO commissioned and provided financial support for this work. WHO acknowledges financial support from the Norwegian Agency for Development Cooperation (NORAD), the Swedish International Development Cooperation Agency (SIDA), the Government of the Grand Duchy of Luxembourg, the Government of Germany (BMG), and the Government of Greece to the WHO Department of Nutrition and Food Safety. REGISTRATION: Our protocol is registered in PROSPERO: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023433123.