Study: Long-Acting GH May Trigger DKA in Children

A newly published case report is drawing attention to a rare but serious metabolic risk associated with long-acting growth hormone (LAGH) therapy — one that clinicians, patients, and caregivers should be aware of before initiating treatment. Published in JCEM Case Reports in July 2026, the study by Mustafa, Hannon, and Fuqua documents a case of severe diabetic ketoacidosis (DKA) occurring in a 13-year-old boy just two days after receiving his first dose of lonapegsomatropin, a long-acting growth hormone formulation — and he had no prior history of diabetes or glucose abnormalities.

What This Study Found

The patient at the center of this case report was a 13-year-old boy diagnosed with hypopituitarism following treatment for a suprasellar nongerminomatous germ cell tumor. He was already receiving standard hormonal replacement therapies — levothyroxine, hydrocortisone, and desmopressin — and presented with obesity but otherwise normal fasting glucose levels prior to starting growth hormone therapy. His hemoglobin A1c (HbA1c) was 5.7%, sitting at the upper boundary of the normal reference range, and he showed no indicators of pre-existing diabetes.

After receiving his first dose of lonapegsomatropin at 0.23 mg/kg/week, he became critically ill within 48 hours. Clinicians documented hyperglycemia, severe metabolic acidosis, and ketonuria — a constellation of findings consistent with DKA. Importantly, laboratory workup revealed that his HbA1c remained at 5.7%, type 1 diabetes autoantibodies were negative, and C-peptide levels were elevated, suggesting that his own insulin-secreting cells were still functional and that this was not a case of underlying autoimmune type 1 diabetes.

The patient recovered fully with insulin and fluid therapy. Following discontinuation of LAGH treatment, he returned to normal glucose levels, with no further metabolic complications reported. The study suggests that the acute and pronounced insulin resistance induced by the long-acting formulation — potentially compounded by his concurrent glucocorticoid therapy and obesity — may have overwhelmed his body's capacity to compensate, precipitating a transient but life-threatening DKA episode.

Clinical Significance

Growth hormone is well understood to exert anti-insulin effects, and mild, transient hyperglycemia has long been recognized as a manageable side effect of standard growth hormone therapy. However, researchers note that DKA in patients without pre-existing diabetes or known glucose abnormalities is considered a rare occurrence — making this case clinically significant and worth careful scrutiny.

What distinguishes long-acting formulations like lonapegsomatropin from traditional daily growth hormone injections is their pharmacokinetic profile. Rather than a brief daily pulse of hormone activity, LAGH formulations are designed to sustain elevated growth hormone concentrations over an entire week. The study suggests this sustained elevation may produce a more prolonged and intense insulin-resistant state than what is seen with short-acting preparations, potentially increasing metabolic risk in susceptible individuals.

The authors identify a cluster of risk factors that may have converged to produce this outcome: the use of a long-acting GH formulation, concurrent glucocorticoid therapy (which itself promotes insulin resistance and glucose dysregulation), obesity, and a borderline HbA1c at the upper limit of normal. No single factor alone may have been sufficient to cause DKA, but together, they appear to have created a critical metabolic vulnerability.

The case underscores the importance of individualized pre-treatment risk assessment before initiating LAGH therapy. The study's authors recommend that close glucose monitoring be considered when starting LAGH treatment in high-risk patients — including those with obesity, concurrent glucocorticoid use, or baseline glucose levels at the higher end of the normal spectrum. Clinicians may also wish to evaluate whether borderline metabolic indicators, even within normal reference ranges, warrant additional precaution in this context.

Current Access and Compliance Context

Long-acting growth hormone formulations like lonapegsomatropin were developed specifically to address one of the most persistent challenges in pediatric endocrinology: medication adherence. Daily subcutaneous injections are burdensome for children and families, and non-adherence is a well-documented problem that can significantly undermine treatment outcomes in growth hormone deficiency. By reducing injection frequency to once weekly, LAGH formulations offer a meaningful practical advantage and have been associated with improved adherence in clinical settings.

This benefit must now be weighed against the emerging picture of metabolic risk that this case report — and the clinical reasoning it presents — helps to clarify. It is worth noting that this is a single case report, not a large-scale clinical trial, and the findings should be interpreted accordingly. The study does not suggest that LAGH therapy is broadly unsafe or that its use should be avoided; rather, it highlights the need for thoughtful patient selection, pre-treatment metabolic screening, and appropriate monitoring protocols, particularly in patients who carry identifiable risk factors.

Prescribing clinicians and patients considering LAGH therapy should engage in a thorough shared decision-making conversation that includes a frank discussion of the metabolic monitoring requirements associated with treatment initiation.

What Patients Should Know

For patients and families navigating growth hormone deficiency treatment decisions, this study provides important context — not a reason for alarm, but a reason for informed preparation. If a child or adolescent is being considered for a long-acting growth hormone formulation, the following points are worth discussing with a qualified endocrinologist:

• Pre-treatment metabolic screening matters. The study suggests that baseline glucose and HbA1c values, even when within normal limits, may be relevant to risk stratification. A borderline HbA1c or other metabolic risk factors may warrant additional monitoring.
• Concurrent medications can interact with GH therapy. Glucocorticoids, which are commonly used in patients with hypopituitarism, may amplify insulin resistance during GH initiation. Clinicians should account for polypharmacy in their risk assessment.
• Monitoring after the first dose is critical. In this case, the patient became critically ill within just 48 hours of his first injection. Patients and caregivers should be educated about the signs and symptoms of hyperglycemia and DKA, particularly in the days immediately following treatment initiation.
• Symptoms of DKA require emergency care. Symptoms can include excessive thirst, frequent urination, nausea, vomiting, abdominal pain, and confusion. If any of these occur after starting growth hormone therapy, emergency medical evaluation is essential.

It is also important to recognize that the patient in this case made a full recovery after discontinuation of GH therapy and appropriate medical treatment — highlighting that prompt recognition and intervention are key.

Conclusion

This 2026 case report from Mustafa, Hannon, and Fuqua offers a valuable clinical signal: long-acting growth hormone therapy, while beneficial for adherence, may carry a risk of acute DKA in high-risk patients — even those without any prior history of diabetes or glucose abnormalities. The study suggests that the intersection of sustained GH-induced insulin resistance, glucocorticoid therapy, and obesity may be sufficient to precipitate this serious complication in vulnerable individuals.

As with all therapeutic decisions, the key lies in individualized assessment, careful monitoring, and open communication between patients and their medical teams. If you or your child is considering growth hormone therapy, working with a knowledgeable, board-certified endocrinologist is essential.

Find a qualified specialist in your area by visiting peptideassociation.org/find-a-doctor.

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 should not be used as the sole basis for any clinical or personal health decision. Always consult a qualified healthcare provider regarding any medical condition or treatment option.

Citation (AMA format):
Mustafa M, Hannon TS, Fuqua JS. Diabetic ketoacidosis induced by long-acting growth hormone in a child without preexisting diabetes. JCEM Case Reports. 2026;(July). doi:10.1210/jcemcr/luag198. PMID: 42488375.