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Clinical Research

Metabolic outcomes and safety of GLP-1 receptor agonists in children and adolescents with obesity: A systematic review and meta-analysis

International Journal of Obesity volume 49, pages 1469–1479 (2025)Cite this article

Subjects

Abstract

Background

Glucagon-like peptide 1 receptor agonists have been proven to be effective in adults with obesity. However, robust evidence on their effects on body weight, obesity-related metabolic changes, and safety in children and adolescents with obesity remains limited, making them a subpopulation with scant treatment options. Therefore, this meta-analysis aimed to determine more precise estimates of the efficacy and safety of glucagon-like peptide-1 agonists in pediatric obesity.

Methods

Three databases were searched (PubMed, Embase, and Cochrane Central Register of Controlled Trials) for trials published until the half of September 2024. The search indexing terms included 3 categories: [1] obesity [2], youth, and [3] glucagon-like peptide-1 receptor agonist (GLP-1 RA). Randomized controlled trials in youth with obesity (age ≤ 18 years) that assessed anthropometric and metabolic parameters were included. A total of 2016 studies were retrieved, and 24 full-text articles were screened. The data were analyzed using both mean differences (MDs) and standardized mean differences (SMDs) with 95% CIs and odds ratios (ORs) with 95% CIs. We applied a random effects model. Our outcomes were body weight (BW), BMI, waist circumference (WC), lipid profile, Hb1Ac, fasting blood glucose (FBG), blood pressure, and side effects.

Results

Eight studies comprised of 715 children and adolescents were included. On average, GLP-1 RA reduced BMI (SMD −0.67; 95% CI −0.8 to −0.41), BW (SMD −0.60; 95% CI −0.89 to −0.44), and WC (SMD −0.40; 95% CI −0.61 to −0.18). Although lipid profiles, HbA1c, and FBG were unaffected, GLP-1 RA was linked to a slight reduction in SBP (SMD −0.20; 95% CI −0.35 to −0.04) and an increase in HR (SMD + 0.26; 95% CI + 0.07 to +0.46), with no significant effect on DBP. Adverse effects, primarily nausea and vomiting, were more common in the intervention group, although trial withdrawal rates remained low.

Conclusions

Within this specific population, GLP-1 RAs exhibit significant reductions in BW, BMI, WC, and SBP. The analyses of lipid profiles, DBP, HbA1c, and FBG showed no significant changes. Also, the administration of these medications is concurrent with an elevated incidence of side effects, which are predominantly gastrointestinal and tolerable.

Trial registration

PROSPERO identifier: CRD42024532845.

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Fig. 1: PRISMA flow chart for the identification, inclusion, and exclusion of studies.
Fig. 2: Risk of bias assessment of the included randomized controlled trials.
Fig. 3: Forest plot from meta-analysis models of GLP-1 RA’s impact on Body Weight, Body Mass Index, and Waist Circumference.
Fig. 4: Forest plot from meta-analysis models of GLP-1 RA’s impact on Lipid Profile.
Fig. 5: Forest plot from meta-analysis models of GLP-1 RA’s impact on Blood Pressure.
Fig. 6: Forest plot from meta-analysis models of GLP-1 RA’s impact on Heart Rate.
Fig. 7: Forest plot from meta-analysis models of GLP-1 RA’s impact on HbA1c and Fasting Blood Glucose.
Fig. 8: Forest plot from meta-analysis models of GLP-1 RA’s impact on Gastrointestinal Adverse Effects.

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Acknowledgements

To conduct this meta-analysis, the first author (L.G.S.P) received a research scholarship granted by the Brazilian National Research Council (CNPq) under the protocol 134326/2024-5.

Funding

Prof. Sposito was supported by a Research Career Awards grant from the Brazilian National Research Council (CNPq) (grant number 304257/2021-4). Cintia Cercato declares having received consulting honoraria from Novo Nordisk, Eli Lilly, Merck, Brace Pharma and Eurofarma.

Author information

Author notes

  1. These authors contributed equally: Luis Gustavo Sedenho-Prado, Louise Buonalumi Tacito Yugar, Cintia Cercato, Andrei C. Sposito.

Authors and Affiliations

  1. School of Medical Sciences, University of Campinas, Campinas, Brazil

    Luis Gustavo Sedenho-Prado, Louise Buonalumi Tacito Yugar, Marília Paiva Martins & Isadora Maria Castilho da Silva Ferreira

  2. Center for Life Sciences Courses, Pontifical Catholic University of Campinas, Campinas, Brazil

    Ana Raquel Whitaker & Daniel Campos Jesus

  3. Department of Statistics, School of Medical Sciences, University of Campinas, Campinas, Brazil

    Cleide Aparecida Moreira Silva

  4. Internal Medicine Department, State University of Campinas, Campinas, Brazil

    Wilson Nadruz

  5. Obesity Unit, Division of Endocrinology and Metabolism, University of São Paulo Medical School Hospital, São Paulo, Brazil

    Cintia Cercato

  6. Atherosclerosis and Vascular Biology Laboratory (Atherolab), State University of Campinas, Campinas, Brazil

    Andrei C. Sposito

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Contributions

LGSP, LBTY, IMCSF, ARW, MPM, and DCJ collected the clinical trial data. CAMS contributed to the statistical analysis of the collected data. LGSP and LBTY drafted the manuscript. ACS and CC reviewed the final manuscript for critical content, had full access to all study data and took responsibility for data integrity and analytical accuracy.

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Correspondence to Andrei C. Sposito.

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Sedenho-Prado, L.G., Yugar, L.B.T., Whitaker, A.R. et al. Metabolic outcomes and safety of GLP-1 receptor agonists in children and adolescents with obesity: A systematic review and meta-analysis. Int J Obes 49, 1469–1479 (2025). https://doi.org/10.1038/s41366-025-01790-w

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