Among four GLP-1 receptor agonists tested in obese or overweight youth, semaglutide produced the greatest reductions in weight, BMI, and BMI z-score while maintaining a favorable safety profile compared to exenatide, liraglutide, and dulaglutide.
953 participants across 11 RCTsThe largest network meta-analysis comparing all four GLP-1 receptor agonists in children and adolescents with obesity
What the researchers found
Semaglutide demonstrated greater efficacy in reducing body weight, BMI, and BMI z-score compared to placebo, exenatide, liraglutide, and dulaglutide in children and adolescents. Semaglutide significantly outperformed exenatide in BMI reduction specifically.
Regarding safety, none of the four GLP-1 RAs were associated with higher risks of diarrhea, headache, or abdominal pain versus placebo. Liraglutide was more likely to cause nausea, vomiting, hypoglycemia, and injection-site reactions compared to both placebo and the other GLP-1 RAs. Semaglutide appeared to be the most effective and safest option overall.
Why it matters
Pediatric obesity affects millions of children worldwide and increases lifetime risk of diabetes, heart disease, and other chronic conditions. While multiple GLP-1 peptide drugs are now available, clinicians lacked head-to-head comparison data to guide treatment selection in young patients. This meta-analysis fills that gap by systematically ranking all four available GLP-1 RAs for both efficacy and safety, directly informing clinical decision-making for a vulnerable population.
How the study worked
Systematic review and network meta-analysis of randomized controlled trials (RCTs). Embase, PubMed, and Scopus were searched through June 2024. Eleven RCTs with 953 participants comparing semaglutide, exenatide, liraglutide, and dulaglutide were included. Primary efficacy outcomes were changes in body weight, BMI, BMI z-score, and waist circumference. Safety outcomes included nausea, vomiting, diarrhea, abdominal pain, injection-site reactions, and hypoglycemia.
What this study cannot tell us
The analysis included 953 participants across 11 trials, which is moderate but still limited for network meta-analysis. Individual trial designs, durations, dosing protocols, and patient characteristics varied. The search was last updated in June 2024, so newer trials may not be included. Long-term safety data (beyond trial durations) in growing children are still limited. Tirzepatide (dual GIP/GLP-1 agonist) was not included, as pediatric data may not have been available at the time of analysis.
How to read the evidence
A network meta-analysis of randomized controlled trials represents one of the highest levels of evidence. The systematic methodology and inclusion of 11 RCTs provide robust comparative data, though the overall pediatric evidence base for GLP-1 RAs is still growing.
When this study was published
Published in 2024 with literature updated through June 2024, this is a current and comprehensive analysis of the pediatric GLP-1 agonist evidence base.
The bigger picture
This study reflects the rapid expansion of peptide-based obesity treatments from adults to pediatric populations. As childhood obesity rates continue to climb globally, the demand for evidence-based pharmacological options grows. This network meta-analysis provides the most comprehensive comparison of GLP-1 peptide agonists in youth to date and will likely influence clinical guidelines and formulary decisions for pediatric weight management programs.
Questions still open
- What are the long-term effects of GLP-1 agonist use on growth, development, and metabolism in children who start these drugs during adolescence?
- How does tirzepatide compare to semaglutide in pediatric obesity — and will it change the ranking?
- Do children regain weight after discontinuing GLP-1 agonists, and if so, what is the optimal duration of treatment?
Common questions
Which GLP-1 drug works best for weight loss in children?
Are GLP-1 drugs safe for children?
Read the original research
Comparative Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists in Children and Adolescents with Obesity or Overweight: A Systematic Review and Network Meta-Analysis.
Pharmaceuticals (Basel, Switzerland), 17(7)
Citation
Liu, Ligang; Shi, Hekai; Shi, Yufei; Wang, Anlin; Guo, Nuojin; Tao, Heqing; Nahata, Milap C. (2024). Comparative Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists in Children and Adolescents with Obesity or Overweight: A Systematic Review and Network Meta-Analysis.. Pharmaceuticals (Basel, Switzerland), 17(7). https://doi.org/10.3390/ph17070828