Research: Long-Acting GH May Trigger DKA in Children

A recently published case report in JCEM Case Reports is drawing attention to a rare but serious metabolic risk associated with long-acting growth hormone (LAGH) therapy: the potential to trigger diabetic ketoacidosis (DKA) in pediatric patients who had no prior history of diabetes. The case, documented by Mustafa, Hannon, and Fuqua (2026), raises important questions about glucose monitoring protocols when initiating newer, extended-release formulations of growth hormone in high-risk children.

What This Study Found

The case involved a 13-year-old boy with hypopituitarism — a condition in which the pituitary gland fails to produce sufficient hormones — resulting from prior treatment of a suprasellar nongerminomatous germ cell tumor. The patient was already receiving hormone replacement therapy including levothyroxine, hydrocortisone, and desmopressin. He also had obesity, but importantly, his fasting glucose was normal and he had no documented history of diabetes or glucose abnormalities before starting growth hormone therapy.

The patient was initiated on lonapegsomatropin, a long-acting formulation of growth hormone, at a dose of 0.23 mg/kg/week. Just two days after receiving his first dose, he presented in critical condition with hyperglycemia, severe metabolic acidosis, and ketonuria — the hallmark triad of DKA.

Diagnostic workup revealed several telling findings. His hemoglobin A1c was 5.7%, sitting at the upper boundary of the normal reference range, suggesting no chronic elevation in blood sugar prior to this event. Autoantibodies associated with type 1 diabetes came back negative, and his C-peptide levels were elevated, indicating that his own pancreas was still capable of producing insulin. These findings, the study suggests, point away from a pre-existing autoimmune or structural diabetes diagnosis and instead implicate the newly introduced growth hormone therapy as the precipitating factor.

After discontinuing lonapegsomatropin and treating the DKA with insulin and intravenous fluids, the patient's glucose levels normalized. He remained normoglycemic following the withdrawal of growth hormone therapy, further supporting the conclusion that the medication played a central role in triggering the acute metabolic crisis.

The researchers propose that the acute and sustained insulin resistance induced by long-acting growth hormone — likely amplified by the patient's concurrent glucocorticoid use and obesity — may have overwhelmed his pancreatic compensatory capacity, precipitating transient but severe DKA even in the absence of pre-existing diabetes.

Clinical Significance

Growth hormone is well-established in its ability to cause transient insulin resistance. This is a recognized, documented side effect of both daily and long-acting GH formulations. However, overt DKA in patients without a prior diabetes diagnosis has historically been considered rare, making this case clinically noteworthy.

What distinguishes long-acting formulations like lonapegsomatropin from traditional daily injections is their pharmacokinetic profile. Rather than producing a brief peak in GH concentration followed by clearance, LAGH formulations are designed to maintain elevated GH levels over an extended period — typically a full week. While this characteristic is precisely what makes them advantageous for patient adherence, it also means the insulin-antagonizing effects of GH are sustained rather than transient.

The authors of the study suggest that this prolonged hormonal exposure, when combined with other insulin resistance-promoting factors such as obesity and exogenous glucocorticoid therapy, may create a compounding metabolic burden that some patients cannot adequately compensate for. In this case, a child whose pancreas appeared structurally and functionally intact was still unable to mount a sufficient insulin response to prevent DKA.

This finding has potential implications for how clinicians approach the initiation of LAGH therapy, particularly in patients who carry multiple metabolic risk factors. The study suggests that close glucose monitoring should be considered when starting long-acting growth hormone therapy in high-risk patients, including those with obesity, those on glucocorticoid therapy, or those with any history of impaired glucose regulation.

Endocrinologists and pediatric specialists may wish to discuss whether baseline metabolic assessments — beyond a standard fasting glucose — are warranted prior to LAGH initiation in certain populations, and whether structured glucose surveillance protocols should be in place during the first days following a first dose.

Current Access and Compliance Context

The development of long-acting growth hormone formulations represents a meaningful advancement in the management of growth hormone deficiency (GHD). Traditional GH replacement therapy requires daily subcutaneous injections, which can be burdensome for pediatric patients and their families. Non-adherence is a well-documented challenge in this population, and suboptimal adherence directly affects treatment outcomes including linear growth velocity and metabolic health.

Lonapegsomatropin, marketed under the brand name SKYTROFA and approved by the U.S. Food and Drug Administration in 2021 for pediatric GHD, was designed specifically to address this adherence gap. A once-weekly injection schedule significantly reduces treatment burden and has demonstrated comparable efficacy to daily formulations in clinical trials.

However, as this 2026 case report illustrates, the extended pharmacokinetic profile that enables weekly dosing also introduces considerations that may not have been fully characterized in pre-approval trial populations. Patients with hypopituitarism, obesity, and concurrent glucocorticoid use — all present in this case — represent a real-world clinical subgroup that may face elevated risk compared to the relatively healthier populations typically enrolled in pivotal registration trials.

This case underscores the importance of ongoing post-market surveillance and real-world reporting to build a more complete picture of LAGH safety across diverse patient populations.

What Patients Should Know

For families of children who have been prescribed long-acting growth hormone therapy, this case report is not cause for alarm, but it is cause for informed conversation with your child's endocrinologist or treating physician. The researchers emphasize that DKA in this context appears to be rare, and growth hormone therapy continues to offer significant, well-documented benefits for children with GHD.

That said, there are several practical considerations that patients and caregivers may wish to raise with their healthcare provider:

• Baseline metabolic assessment: Ask whether your child's glucose metabolism has been thoroughly evaluated before starting LAGH therapy, particularly if they have obesity or are on other medications that affect blood sugar.
• Early monitoring after first dose: This case suggests that adverse metabolic effects may emerge within just 48 hours of the first injection. Understanding what symptoms to watch for — including excessive thirst, frequent urination, nausea, vomiting, and fatigue — and when to seek emergency care is critically important.
• Medication interactions: If your child is also taking glucocorticoids (such as hydrocortisone) for adrenal insufficiency or another condition, discuss with your provider how this combination may affect glucose regulation.
• Shared decision-making: The choice between daily and long-acting GH formulations involves weighing adherence benefits against individual risk profiles. This case adds important nuance to that conversation for higher-risk patients.

The study serves as a reminder that even therapies with well-established safety profiles can produce unexpected outcomes in individual patients, particularly when multiple metabolic risk factors are present simultaneously.

Conclusion

The 2026 case report by Mustafa, Hannon, and Fuqua provides a compelling, evidence-based signal that long-acting growth hormone therapy may carry a risk of DKA in pediatric patients without prior diabetes, particularly when compounding metabolic risk factors are present. While this represents a rare outcome, the severity of DKA and the speed of its onset — just two days after the first dose — highlight the need for vigilant clinical monitoring protocols and individualized risk assessment.

As long-acting peptide therapies continue to evolve and expand in clinical use, cases like this contribute essential real-world data to help clinicians, patients, and regulatory bodies better understand their full risk-benefit profiles.

If you have questions about growth hormone therapy, peptide-based treatments, or how to find a qualified specialist who can provide individualized guidance, we encourage you to visit peptideassociation.org/find-a-doctor to connect with a knowledgeable healthcare provider in your area.

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Medical Disclaimer: This article is intended for educational and informational purposes only and does not constitute medical advice, diagnosis, or treatment recommendations. The content is based on a published case report and reflects the findings and opinions of the cited study authors. Always consult a qualified healthcare professional before making any decisions regarding medical treatment, including the initiation, continuation, or discontinuation of any therapy. Individual medical circumstances vary, and only a licensed clinician familiar with your specific situation can provide appropriate guidance.

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Citation: Mustafa M, Hannon TS, Fuqua JS. Diabetic ketoacidosis induced by long-acting growth hormone in a child without preexisting diabetes. JCEM Case Reports. 2026 Jul. PMID: 42488375. DOI: 10.1210/jcemcr/luag198