PRISMA 2020 checklist.

<div> Background Obesity significantly impacts the health outcomes of children and adolescents, necessitating a comprehensive study to evaluate the effects of various anti-obesity medications (AOMs) on weight-related and metabolic outcomes. Methods PubMed, EMBASE, and CENTRAL were searched for studies published up to January 3, 2024. We performed a network meta-analysis on randomized clinical trials that compared various treatments for pediatric and adolescent obesity, such as phentermine/topiramate, semaglutide, exenatide, liraglutide, topiramate, metformin, fluoxetine, metformin/fluoxetine, sibutramine, and orlistat. The study evaluated body mass index (BMI), BMI percentage change, weight, BMI-SDS, waist circumference, metabolic, anthropometric, and safety outcomes. Results The study gathered 2733 studies, including 30 articles that involved 3822 participants. The results of our research showed that PHEN/TPM was better at lowering BMI than exenatide, liraglutide, metformin, fluoxetine, Met/Flu, topiramate, orlistat, and sibutramine, with mean differences (MD) ranging from −10.29 to −1.28. Additionally, semaglutide demonstrated superior efficacy over other AOMs (MD ranged from −8.28 to −1.24). Various levels of certainty, ranging from very low to moderate, supported the findings. Furthermore, semaglutide demonstrated superior efficacy over exenatide (MD-12.43, 95% CI −23.95 to −0.30) regarding percentage change in BMI. Semaglutide also showed enhanced weight reduction effectiveness compared to seven other AOMs except for PHEN/TPM (MD ranging from −15.56 to −12.65). Similarly, PHEN/TPM displayed greater weight reduction effectiveness than seven other AOMs, except for semaglutide (MD ranged from −12.17 to −9.27). Moreover, semaglutide proved more effective in decreasing waist circumference when compared with other AOMs apart from PHEN/TPM (MD ranged from −11.61 to −6.07). Similarly, we found that PHEN/TPM, excluding semaglutide and sibutramine, was more effective in reducing waist circumference (MD ranged from −8.64 to −5.51). Conclusions The study found that semaglutide outperformed other AOMs in reducing BMI and additional weight-related outcomes in children and adolescents with obesity, while PHEN/TPM showed comparable efficacy. </div>