Systematic Reviews
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jul 15, 2025; 16(7): 106890
Published online Jul 15, 2025. doi: 10.4239/wjd.v16.i7.106890
Pharmacological management of type 2 diabetes mellitus in children and adolescents: A systematic review and network meta-analysis
Charles A Gagnon, Katherine Buchanan, Jill M Deaver, Jessica A Schmitt, Ian M Lahart, Sahana Shetty, Ambika P Ashraf, Joseph M Pappachan
Charles A Gagnon, Katherine Buchanan, Marnix E Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, United States
Jill M Deaver, Lister Hill Library of the Health Sciences, University of Alabama at Birmingham, Birmingham, AL 35233, United States
Jessica A Schmitt, Ambika P Ashraf, Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233, United States
Ian M Lahart, Department of Health & Wellbeing, University of Wolverhampton, Wolverhampton WV1 1 LY, United Kingdom
Sahana Shetty, Joseph M Pappachan, Department of Endocrinology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
Joseph M Pappachan, Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, Greater Manchester, United Kingdom
Co-corresponding authors: Ambika P Ashraf and Joseph M Pappachan.
Author contributions: Gagnon CA and Buchanan KV contributed to the data collection, curation, quality assessment of studies and writing of the initial manuscript; Deaver JM performed the literature search with filtering of duplicate and grey literature; Schmitt JA supervised the data collection, curation and quality assessment; Shetty S and Lahart IM contributed to the data acquisition, statistical analyses and the review of the literature search; Pappachan JM and Ashraf AP have conceived the idea, performed the design, assisted the data acquisition, and implementation of the study with supervision of the entire manuscript preparation and editing of the work in the final form as co-corresponding authors; Ashraf AP filtered the data after literature search, liaising with Gagnon CA and Buchanan KV, and drafted the early version of the manuscript with a focus on the impact of various pharmacotherapeutic agents on management of T2DM in children and adolescents; Pappachan JM was instrumental and responsible for data analysis, interpretation, and figure plotting liaising with IM Lahart, and supervised a comprehensive literature search, preparation and submission of the current version of the manuscript with a focus on how pharmacotherapy improved pediatric diabesity among children. This collaboration between Ashraf AP and Pappachan JM was crucial for the publication of this manuscript. All authors contributed to the quality and professional revision of the manuscript in its final form.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Joseph M Pappachan, MD, MRCP, FRCP, Professor, Senior Researcher, Faculty of Science, Manchester Metropolitan University, All Saints Building, Manchester M15 6BH, Greater Manchester, United Kingdom. drpappachan@yahoo.co.in
Received: March 10, 2025
Revised: May 7, 2025
Accepted: June 6, 2025
Published online: July 15, 2025
Processing time: 127 Days and 11.8 Hours
Abstract
BACKGROUND

The incidence of type 2 diabetes mellitus (T2DM) in children and adolescents is increasing, yet there is limited information on the available pharmacological interventions to combat T2DM and prevent associated comorbidities.

AIM

To assess the effectiveness of current pharmacological treatments in managing T2DM in children and adolescents. The protocol of the study was registered in PROSPERO (CRD42022382165).

METHODS

Searches were performed in PubMed, EMBASE, Scopus, and ClinicalTrials.gov for publications between 1990 to September 2024 without language restrictions. Randomized control trials (RCTs) of pharmacotherapy in children and adolescents with T2DM (aged < 19 years) were included. The primary outcome was a change in glycated hemoglobin (HbA1c) from baseline to follow-up. Secondary outcomes were changes in body weight, body mass index (BMI), total cholesterol, triglycerides, high density lipoprotein, and low-density lipoprotein from baseline, and incidence of adverse events during study periods. Screening, full-text review, data extraction, and assessments of risk of bias were done by two reviewers. Conflicts on each step were resolved by a third reviewer. Data analysis was performed using Review Manager Version 6.5 (RevMan 6.5) and ‘R’ software via RStudio, ‘meta’ and ‘netmeta’.

RESULTS

A total of 12 studies having low to moderate risk of bias with 1658 participants, and follow-up duration 12-52 weeks were included. In our network meta-analysis, compared to control(s), the reduction of HbA1c was significantly larger for dulaglutide [mean difference (MD), 95% confidence interval: -1.20, -2.12 to -0.28], followed by dapagliflozin (-0.94, -1.44 to -0.44), liraglutide (-0.91, -1.37 to -0.45), empagliflozin (-0.87, -1.40 to -0.34), exenatide (-0.59, -1.07 to -0.11) and linagliptin (-0.45, -0.87 to -0.02) while other drugs had little or no effect. While liraglutide was associated with a change in body weight [MD -2.41 (-4.68, -0.14) kg], no other drug treatment was associated with significant changes in body weight, BMI, and lipids. Apart from level 1 hypoglycemia with liraglutide [risk difference (RD): 0.20, 0.04-0.37] and minor adverse events with dulaglutide (RD: 0.24, 0.08-0.40), no other treatment was associated with excess risk of hypoglycemia or minor or major adverse events.

CONCLUSION

Pharmacotherapy of T2DM with dulaglutide, dapagliflozin, liraglutide, empagliflozin, exenatide, and linagliptin in children is associated with modest reduction of HbA1c. Larger RCTs with longer follow-up durations are needed to guide better therapeutic decision making.

Keywords: Type 2 diabetes mellitus; Pharmacotherapy; Children; Adolescents; Obesity; Diabesity; Glycemic control

Core Tip: Although the prevalence of obesity and type 2 diabetes are increasing among children, there is only limited evidence on pharmacotherapeutic interventions to address the issue. Twelve studies including 1658 participants (follow-up: 12-52 weeks) in this meta-analysis revealed that dulaglutide, dapagliflozin, liraglutide, empagliflozin, exenatide, and linagliptin treatment resulted in mean glycated hemoglobin reductions of -1.20%, -0.94%, -0.91%, -0.87%, -0.59% and -0.45% respectively, while other drugs had little/no effect. No drug treatment conferred significant changes in body weight (except liraglutide), body mass index, and lipids. Except for mild hypoglycemia with liraglutide and minor adverse events with dulaglutide use, pharmacotherapy was generally safe.