Semaglutide and Phentermine-Topiramate Lead Largest BMI Reductions in Pediatric Obesity

The global rise in childhood and adolescent overweight and obesity represents a critical public health challenge, driving significant long-term health risks. While lifestyle interventions are foundational, they often prove insufficient for sustained weight management in many young patients. This creates a pressing need for effective pharmacologic adjuncts that can safely and significantly reduce weight. Understanding the comparative efficacy and safety of available drug therapies, such as GLP-1 receptor agonists and combination drugs, is crucial for guiding clinical decisions and improving outcomes in this vulnerable population.

A systematic review and network meta-analysis of 41 randomized controlled trials (N=3923) compared pharmacologic interventions for pediatric obesity. Researchers sourced RCTs from PubMed, Embase, Cochrane Library (CENTRAL), WHO ICTRP, and ClinicalTrials.gov from inception to July 28, 2025. A frequentist network meta-analysis using a random-effects model was performed. The primary endpoint was reduction in the 95th BMI percentile compared to lifestyle modification alone, with secondary endpoints including the number of additional patients achieving ≥5% and ≥10% BMI reduction.

Compared with lifestyle modification alone, semaglutide demonstrated the most substantial reduction in the 95th BMI percentile. The analysis showed a mean difference (MD) of -20.40% (95% CI -24.22 to -16.58) for semaglutide. This translated to an additional 500 patients per 1000 person-years achieving ≥5% BMI reduction and 399 patients per 1000 person-years achieving ≥10% BMI reduction. Phentermine-topiramate exhibited the next largest effect, with an MD of -18.35% (95% CI -22.26 to -14.45), leading to 554 and 734 additional responders per 1000 person-years for ≥5% and ≥10% BMI reduction, respectively. Liraglutide and exenatide also significantly reduced the 95th BMI percentile compared to lifestyle modification alone, although their reductions were smaller than those observed with semaglutide and phentermine-topiramate. The study highlighted phentermine-topiramate's favorable tolerability profile. > Semaglutide produced the largest reduction in the 95th BMI percentile (MD -20.40%, 95% CI -24.22 to -16.58), with an additional 500 and 399 patients per 1000 person-years achieving ≥5% and ≥10% BMI reduction, respectively.