GLP-1 Receptor Agonists and Dual GIP/GLP-1 Receptor Agonists in Children and Adolescents with Obesity: Clinical Outcomes and the Impact of Nutritional and Behavioral Co-Interventions-A Systematic Review.
This systematic review examined the clinical outcomes of GLP-1 receptor agonists (GLP-1 RAs) and dual GIP/GLP-1 receptor agonists in children and adolescents (aged 6–19 years) with overweight or obesity, with or without type 2 diabetes. Researchers searched PubMed, Scopus, and ClinicalTrials.gov following PRISMA 2020 guidelines, ultimately analyzing 15 studies (12 interventional, 3 observational) comprising 1,448 participants across six agents: liraglutide, exenatide, semaglutide, dulaglutide, tirzepatide, and lixisenatide. Study durations ranged from 6 to 68 weeks. The review found that BMI reductions varied across agents and study designs, with semaglutide trials reporting reductions of up to –16.1%. A key finding was the substantial heterogeneity in how concomitant lifestyle interventions were reported—ranging from general dietary advice to structured multidisciplinary programs—making it impossible to isolate the independent contributions of pharmacological versus behavioral components. The authors conclude that while GLP-1 RAs appear to be a promising therapeutic option in this population, the evidence base is limited by inconsistent lifestyle co-intervention reporting. They call for standardized reporting frameworks (e.g., TIDieR), validated behavioral measures, and factorial or stratified study designs to disentangle drug and lifestyle effects in future pediatric trials.
Why this grade: This is a systematic review synthesizing 15 heterogeneous pediatric studies; it does not generate primary data and its own graded conclusions are constrained by the inconsistent reporting quality of the included studies.
Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for the treatment of type 2 diabetes (T2D), are increasingly used for the management of overweight and obesity in children and adolescents. However, the impact of concomitant lifestyle interventions, which vary in scope, structure, and intensity, remains unclear. Methods: A systematic search of PubMed, Scopus, and ClinicalTrials.gov was conducted from April to December 2025 (last update: 12 December 2025), in accordance with the PRISMA 2020 statement. Randomized and observational studies including patients aged 6-19 years with overweight or obesity, with or without T2D, treated with GLP-1 RAs or dual GIP/GLP-1 agonists, were included. Anthropometric outcomes, metabolic parameters, and the scope and structure of concomitant nutritional and behavioral interventions were assessed. Results: Fifteen studies (12 interventional [RCT/non-RCT] and 3 observational), including 1448 participants, were analyzed: liraglutide ( n = 6), exenatide ( n = 5), semaglutide ( n = 1), dulaglutide ( n = 1), tirzepatide ( n = 1), and lixisenatide ( n = 1). Intervention duration ranged from 6 to 68 weeks. Reported BMI reductions varied across studies and pharmacological agents, with semaglutide trials reporting reductions of up to -16.1%. Lifestyle interventions were heterogeneously reported, ranging from general dietary advice to structured, multidisciplinary programs including nutritional counseling, physical activity, and behavioral or family support. Due to heterogeneity in study design and reporting, the independent contribution of lifestyle interventions could not be determined. Conclusions: Available evidence suggests that GLP-1 RAs may represent an effective therapeutic option for children and adolescents with obesity and metabolic disorders. However, available evidence is largely derived from studies incorporating inconsistently reported lifestyle interventions, limiting the ability to disentangle pharmacological and lifestyle effects. Standardized reporting and studies specifically designed to assess their independent and combined effects are needed. Future research should standardize the reporting of lifestyle protocols (e.g., using TIDieR), incorporate validated measures of eating behavior, food preferences, and dietary intake, and use designs (e.g., factorial or stratified randomization of lifestyle intensity) that allow for the pharmacological and behavioral contributions to be quantified separately. This review highlights a critical and previously underexplored methodological gap regarding the structure and reporting of lifestyle co-interventions in pediatric GLP-1 trials.
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