What Pediatric Endocrinologists Need to Know About Diabetes in the Age of GLP-1s

GLP-1 receptor agonists such as Ozempic (semaglutide) offer new opportunities for managing pediatric diabetes and obesity. These medications target insulin resistance and related comorbidities, but their use raises questions about safety, access and ethical considerations.

In the following interview, Leena Mamilly, MD, and Rohan K. Henry, MD, pediatric endocrinology experts at Nationwide Children’s Hospital, explore how these therapies fit into current care practices and what clinicians need to know to use them effectively.

Q: How Do GLP-1 Receptor Agonists Work in Pediatric Diabetes Care?
GLP-1 receptor agonists provide targeted control for type 2 diabetes and obesity in children by delaying gastric emptying, slowing glucose absorption; reducing appetite and promoting weight loss, as well as lowering glucagon levels, which improves blood sugar control. These mechanisms address insulin resistance more directly than traditional treatments such as metformin, which primarily reduces glucose production in the liver.

Q: When Should Clinicians Choose GLP-1 Agonists for Pediatric Patients?

Metformin remains the first-line treatment for pediatric type 2 diabetes due to its efficacy, safety and affordability. However, when HbA1c goals (typically <6.5%) are unmet or metformin causes side effects, GLP-1 receptor agonists such as dulaglutide (Trulicity) or liraglutide (Victoza) may be added. Dulaglutide’s once-weekly dosing is particularly convenient for families.

Before prescribing a GLP-1 agonist for diabetes control, clinicians should rule out contraindications such as a family history of medullary thyroid carcinoma to ensure safe use.

Q: What Are the Clinical Outcomes of GLP-1 Receptor Agonists?
In practice, GLP-1 receptor agonists can lower HbA1c and, in some cases, eliminate the need for insulin. Weight loss achieved with these medications may result in improvements in blood pressure, fatty liver disease, and other obesity-related conditions, particularly in cases where these conditions are driven by insulin resistance. Such improvements simplify treatment regimens and may enhance adherence.

Common side effects, such as nausea and vomiting, typically resolve over time. Rare risks, including gallbladder disease and pancreatitis, highlight the need for monitoring and patient education.

Q: What Challenges Arise with Using GLP-1 Agonists in Pediatrics?
Ethical concerns arise from the lack of long-term safety data, highlighting the need for further research as the side effect profile continues to evolve with broader use. Additionally, insurance coverage remains a major obstacle, particularly for Medicaid patients, as weight management medications are often excluded. Advocacy is crucial to ensure equitable access.

Q: How Do GLP-1 Receptor Agonists Help Manage Comorbidities in Obese Children?
GLP-1 receptor agonists assist in managing obesity-related conditions, such as polycystic ovarian syndrome, obstructive sleep apnea, and fatty liver disease. While evidence in adults strongly supports cardiovascular benefits and has shaped treatment guidelines, further research is required to determine if similar effects are observed in pediatric populations.

Q: What Monitoring and Adjustments Are Needed for Safe Use of GLP-1 Agonists?

Regular monitoring is essential for safety and effectiveness. HbA1c should be checked every three months. While additional tests, such as glucose levels, kidney function, and pancreatic enzymes, may occasionally be necessary to monitor for adverse effects like pancreatitis, they are not routinely required. Restarting treatment at the lowest dose after interruptions can help minimize side effects.

Q: What’s Next for GLP-1 Receptor Agonists in Pediatric Diabetes Care?

Ongoing research is exploring new formulations, such as oral semaglutide, and dual agonists such as tirzepatide. Trials focusing on prediabetes and other metabolic conditions could expand treatment options, offering clinicians more tools to manage pediatric diabetes effectively.

Conclusion
GLP-1 receptor agonists represent a significant advancement in managing pediatric diabetes and obesity, providing options that directly address insulin resistance, promote weight loss and reduce risks from related comorbidities. However, their integration into pediatric care requires careful consideration of long-term safety, access barriers and ethical concerns. By combining careful patient selection, regular monitoring and advocacy for equitable access, health care providers can maximize the potential of these therapies to improve outcomes. Continued innovation and research into new formulations and expanded indications promise to further enhance the tools available to clinicians, paving the way for better care and quality of life for children with diabetes and obesity.

References

1. American Diabetes Association Professional Practice Committee. 14. Children and Adolescents: Standards of Care in Diabetes-2025. Diabetes Care. 2025 Jan 1;48(Supplement_1):S283-S305.
2. Arslanian SA, Hannon T, Zeitler P, Chao LC, Boucher-Berry C, Barrientos-Pérez M, Bismuth E, Dib S, Cho JI, Cox D; AWARD-PEDS Investigators. Once-Weekly Dulaglutide for the Treatment of Youths with Type 2 Diabetes. N Engl J Med. 2022 Aug 4;387(5):433-443.
3. Weghuber D, Barrett T, Barrientos-Pérez M, Gies I, Hesse D, Jeppesen OK, Kelly AS, Mastrandrea LD, Sørrig R, Arslanian S; STEP TEENS Investigators. Once-Weekly Semaglutide in Adolescents with Obesity. N Engl J Med. 2022 Dec 15;387(24):2245-2257.
4. Hampl SE, Hassink SG, Skinner AC, Armstrong SC, Barlow SE, Bolling CF, Avila Edwards KC, Eneli I, Hamre R, Joseph MM, Lunsford D, Mendonca E, Michalsky MP, Mirza N, Ochoa ER, Sharifi M, Staiano AE, Weedn AE, Flinn SK, Lindros J, Okechukwu K. Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity. Pediatrics. 2023 Feb 1;151(2):e2022060640. Erratum in: Pediatrics. 2024 Jan 1;153(1):e2023064612.
5. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsbøll T; SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-1844.