Pharmacotherapy for Children and Adolescents With Overweight or Obesity: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Semaglutide produced the largest reduction in the 95th BMI percentile among 41 trials in children and adolescents with overweight or obesity, followed by phentermine-topiramate; liraglutide and exenatide also reduced it more than lifestyle modification alone. The authors judged phentermine-topiramate, based on tolerability, as potentially the best adjunct to lifestyle interventions.

Systematic review — Systematic review and network meta-analysis of RCTs. Population: Children and adolescents with overweight or obesity. Sample size: 3923 participants across 41 RCTs. Interventions: Semaglutide; Phentermine-topiramate; Liraglutide; Exenatide.

The network meta-analysis included 41 RCTs (N=3923). Compared with lifestyle modification alone, semaglutide produced the largest reduction in the 95th BMI percentile (MD -20.40%, 95% CI -24.22 to -16.58), with 500 and 399 additional patients per 1000 person-years achieving ≥5% and ≥10% BMI reduction. Phentermine-topiramate showed the next largest reduction (MD -18.35%, 95% CI -22.26 to -14.45), with 554 and 734 additional responders per 1000 person-years. Liraglutide and exenatide also significantly reduced the 95th BMI percentile, but less than semaglutide and phentermine-topiramate. The authors concluded that phentermine-topiramate, given its favourable tolerability, may be the optimal adjunct to lifestyle interventions.

This paper is directly relevant to researchers working on semaglutide and liraglutide because it places these agents against phentermine-topiramate and exenatide in pediatric obesity, giving comparative effect sizes on the 95th BMI percentile and responder rates. It does not establish dosing, long-term safety, or outcomes beyond BMI-reduction endpoints in this population.

Key findings

• Semaglutide produced the largest reduction in the 95th BMI percentile versus lifestyle modification alone (MD -20.40%, 95% CI -24.22 to -16.58).
• Semaglutide was associated with 500 and 399 additional patients per 1000 person-years achieving ≥5% and ≥10% BMI reduction, respectively.
• Phentermine-topiramate showed the next largest reduction in the 95th BMI percentile (MD -18.35%, 95% CI -22.26 to -14.45).
• Phentermine-topiramate was associated with 554 and 734 additional responders per 1000 person-years.
• Liraglutide and exenatide significantly reduced the 95th BMI percentile compared with lifestyle modification alone, but less than semaglutide and phentermine-topiramate.
• The meta-analysis included 41 RCTs with 3923 participants.

Limitations

• No limitations are stated in the abstract.
• Network meta-analysis relies on indirect comparisons and consistency assumptions.
• Results are based on aggregate trial data, not individual patient-level responses or adverse effects.

The record

• Journal: Diabetes, obesity & metabolism 28(9): 8145-8156
• Published: 2026-06-17
• PMID: 42310900 — DOI: 10.1111/dom.70986
• MeSH terms: Humans, Weight Loss, Phentermine, Anti-Obesity Agents, Body Mass Index, Adolescent, Child, Overweight, Randomized Controlled Trials as Topic, Pediatric Obesity, Liraglutide, Topiramate, Exenatide, Semaglutide
• Funding: Central Hospital of Karamay; The Second Group of Tianshan Talent Training Program
• Author countries: China

Peptide profiles: Semaglutide, Liraglutide.

All indexed evidence: Semaglutide trials & papers, Liraglutide trials & papers.

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