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

Author/s: 
Ke-wen Wan, Evander Fung-chau Lei, Ying Liu, Asefa Adimasu Taddese, Patrick lp, Gabriel Torbahn, Daniel Weghuber, Wendy Y. Huang, Bjorn T.Tam

Abstract
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.

Keywords 
pediatric obesity pharmacotherapy meta-analysis

Managing obesity in children: a clinical practice guideline

Author/s: 
Geoff D C Ball, Roah Merdad, Catherine S Birken, Tamara R Cohen, Brenndon Goodman, Stasia Hadjiyannakis

Background: Obesity is a complex, chronic, stigmatized disease whereby abnormal or excess body fat may impair health or increase the risk of medical complications, and can reduce quality of life and shorten lifespan in children and families. We developed this guideline to provide evidence-based recommendations on options for managing pediatric obesity that support shared decision-making among children living with obesity, their families, and their health care providers.

Methods: We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We used the Guidelines International Network principles to manage competing interests. Caregivers, health care providers, and people living with obesity participated throughout the guideline development process, which optimized relevance. We surveyed end users (caregivers, health care providers) to prioritize health outcomes, completed 3 scoping reviews (2 on minimal important difference estimates; 1 on clinical assessment), performed 1 systematic review to characterize families' values and preferences, and conducted 3 systematic reviews and meta-analyses to examine the benefits and harms of behavioural and psychological, pharmacologic, and surgical interventions for managing obesity in children. Guideline panelists developed recommendations focused on an individualized approach to care by using the GRADE evidence-to-decision framework, incorporating values and preferences of children living with obesity and their caregivers.

Recommendations: Our guideline includes 10 recommendations and 9 good practice statements for managing obesity in children. Managing pediatric obesity should be guided by a comprehensive child and family assessment based on our good practice statements. Behavioural and psychological interventions, particularly multicomponent interventions (strong recommendation, very low to moderate certainty), should form the foundation of care, with tailored therapy and support using shared decision-making based on the potential benefits, harms, certainty of evidence, and values and preferences of children and families. Pharmacologic and surgical interventions should be considered (conditional recommendation, low to moderate certainty) as therapeutic options based on availability, feasibility, and acceptability, and guided by shared decision-making between health care providers and families.

Interpretation: This guideline will support children, families, and health care providers to have informed discussions about the balance of benefits and harms for available obesity management interventions to support value- and preference-sensitive decision-making

Keywords 
obesity children pediatric obesity
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