Obesity Management Pharmacotherapies and Lifestyle Treatment for Pediatric Obesity Management: A Systematic Review and Network Meta-Analysis.

Importance: Pediatric obesity is a global health challenge. Although health behavior and lifestyle treatment (HBLT) is foundational, the comparative effectiveness of HBLT, various pharmacotherapies, and their combinations remains unclear. Objective: To compare the effectiveness of obesity management pharmacotherapies, structured lifestyle treatment, and their combinations on weight management outcomes in children and adolescents living with obesity. Data Sources: A systematic search was conducted in 4 electronic databases (Embase, CENTRAL, PsycINFO, and PubMed) from inception to June 17, 2025. Data Selection: Randomized clinical trials (RCTs) involving children and adolescents (aged 10-19 years) with obesity were selected. Interventions included lifestyle treatment (HBLT and counseling), obesity management pharmacotherapies (glucagon-like peptide-1 receptor agonists, metformin, orlistat, phentermine topiramate), or their combination vs control. Data Extraction and Synthesis: Data were extracted and validity assessed according to PRISMA guidelines. A random-effects network meta-analysis was used to pool data. Meta-regression was used to explore outcome moderators. Main Outcomes and Measures: Primary outcomes were body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and BMI z score; secondary outcomes included waist circumference (WC), fat mass (FM), and lean mass (LM). Results: A total of 42 RCTs with 3835 participants (median [IQR] age, 14.5 [13.3-15.1] years; 2270 female [59.2%]) were included. Treatments combining pharmacotherapy and lifestyle treatment demonstrated the greatest efficacy across all adiposity-related outcomes. Semaglutide plus counseling was associated with the largest BMI reduction (mean difference, -8.31; 95% CI, -12.33 to -4.28) and BMI z score reduction (mean difference, -1.80; 95% CI, -2.39 to -1.21), although this estimate was based on a limited number of studies. All pharmacological treatments were more effective when paired with lifestyle treatment, associated with significantly greater BMI and BMI z score reductions than the same medications alone. Based on the primary analysis, HBLT as monotherapy was associated with substantial decreases in BMI (mean difference, -3.85; 95% CI, -4.91 to -2.80) and BMI z score (mean difference, -0.89; 95% CI, -1.17 to -0.61) vs control. Conclusions and Relevance: Finding of this systematic review and network meta-analysis suggest that combining lifestyle treatment with obesity management medications was associated with the greatest short-term (typically 6 to 12 months) weight reduction in adolescents with obesity. HBLT remained an indispensable component of any effective weight management, delivering meaningful weight loss and healthier body composition on its own. Combined with lifestyle treatment, pharmacotherapy was a key component, not solely an adjunct, associated with the greatest BMI and BMI z score improvements, and long-term sustainability and safety were monitored.