Long-Acting Growth Hormone & DKA Risk: New Research

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

What This Study Found

The patient at the center of this report was a 13-year-old male with hypopituitarism, obesity, and a history of a suprasellar nongerminomatous germ cell tumor. He was already receiving hormonal replacement therapies — levothyroxine, hydrocortisone, and desmopressin — and had a normal fasting glucose prior to starting growth hormone therapy. His hemoglobin A1c was 5.7%, placing him at the upper boundary of normal, and he had no known diabetes or insulin resistance diagnosis.

Two days after receiving his first dose of lonapegsomatropin at 0.23 mg/kg/week, the adolescent presented critically ill. Laboratory findings confirmed hyperglycemia, severe metabolic acidosis, and ketonuria — a clinical picture consistent with DKA. Importantly, type 1 diabetes autoantibodies were negative, and his C-peptide levels were elevated, indicating that his pancreatic beta cells were still capable of producing insulin. This finding effectively ruled out autoimmune type 1 diabetes as the underlying cause.

The DKA resolved with standard treatment — intravenous insulin and fluid therapy. After the long-acting growth hormone was discontinued, the patient returned to normal blood glucose levels without any ongoing diabetes management. The study suggests that the acute, pronounced insulin resistance triggered by the long-acting formulation — possibly compounded by his concurrent glucocorticoid therapy and obesity — was sufficient to overwhelm his body's insulin response and precipitate a life-threatening metabolic crisis.

Clinical Significance

Growth hormone therapy is well-established in its ability to induce transient insulin resistance and mild hyperglycemia. These effects are considered recognized and generally manageable side effects. However, the researchers highlight that full-blown DKA in a patient without preexisting diabetes is a rare and underappreciated complication, particularly in the context of newer long-acting formulations.

Long-acting growth hormone products like lonapegsomatropin are engineered to release growth hormone gradually over a week, improving convenience and adherence compared to daily injections. But this pharmacokinetic profile may also mean a more sustained and concentrated insulin-antagonizing effect in the early days after the first dose. According to the study, this acute insulin resistance appears to have been the primary driver of DKA in this patient.

The case also underscores a potentially important interaction between multiple metabolic risk factors. The patient had three compounding variables: obesity (which independently contributes to insulin resistance), ongoing glucocorticoid replacement (hydrocortisone is known to raise blood glucose), and the acute insulin resistance induced by the LAGH therapy. The researchers suggest that the convergence of these factors may have pushed the patient past a metabolic threshold his body could not manage without intervention.

The authors conclude that close glucose monitoring should be considered when initiating LAGH therapy in high-risk patients — a population that may include those with obesity, concurrent glucocorticoid use, a borderline A1c, or other metabolic vulnerabilities. This case serves as a clinical signal, even if it represents a single reported instance, that the risk profile for LAGH therapy may warrant additional scrutiny in certain pediatric and adolescent populations.

Current Access and Compliance Context

Long-acting growth hormone formulations represent a significant advancement in the management of growth hormone deficiency (GHD). Traditional recombinant human growth hormone (rhGH) requires daily subcutaneous injections, a regimen that can be burdensome for pediatric patients and their families. Adherence to daily injection schedules has historically been a challenge in this population, with missed doses directly impacting growth outcomes.

The development of weekly formulations like lonapegsomatropin was specifically intended to address this compliance barrier. By reducing the injection frequency to once weekly, LAGH products have demonstrated improved adherence rates and comparable — or in some studies, superior — growth outcomes relative to daily rhGH. For many children with GHD, this represents a meaningful quality-of-life improvement.

However, the expanded use of these therapies means that a broader range of patients — including those with more complex medical histories and comorbidities — are now initiating LAGH treatment. This case report serves as a timely reminder that improved convenience should not come at the expense of adequate pre-treatment risk assessment and post-initiation monitoring protocols. As LAGH therapies become more widely prescribed, the clinical community may need to develop clearer guidelines for metabolic monitoring in higher-risk subgroups.

What Patients Should Know

If you or your child is being considered for long-acting growth hormone therapy, this research highlights the importance of a thorough pre-treatment evaluation. The study suggests that patients with certain risk factors — including obesity, concurrent steroid use, or borderline blood glucose levels — may face an elevated risk of acute metabolic complications when starting LAGH therapy.

This does not mean that growth hormone therapy is unsafe or should be avoided. Rather, the findings suggest that close monitoring in the days and weeks following the first dose may be warranted for some patients. Blood glucose checks, either at home or in a clinical setting, could help detect early signs of hyperglycemia before a more serious complication develops.

Patients and caregivers should discuss the following with their healthcare provider before beginning LAGH therapy:

• Pre-treatment glucose screening: A fasting glucose, hemoglobin A1c, and potentially an oral glucose tolerance test may help identify underlying insulin resistance before treatment starts.
• Review of concurrent medications: Glucocorticoids, antipsychotics, and other medications that affect insulin sensitivity should be evaluated in the context of LAGH initiation.
• Monitoring plan: Ask your provider what glucose monitoring will look like after the first dose and who to contact if symptoms of hyperglycemia arise.
• Warning signs of DKA: Symptoms including excessive thirst, frequent urination, nausea, vomiting, abdominal pain, and unusual fatigue should prompt immediate medical evaluation.

It is also worth noting that in this reported case, the DKA was successfully treated and the patient recovered fully after discontinuing the LAGH therapy. This outcome reflects the importance of prompt recognition and medical response.

Conclusion

This 2026 case report from Mustafa, Hannon, and Fuqua is an important contribution to the growing body of literature on long-acting growth hormone therapy and its metabolic effects. While DKA as a complication of LAGH initiation appears to be rare, the case makes a compelling argument for individualized risk assessment and proactive glucose monitoring — particularly in patients with obesity, glucocorticoid use, or other metabolic vulnerabilities.

As the use of LAGH formulations continues to expand, both clinicians and patients benefit from staying informed about the full spectrum of potential effects. Evidence-based guidance from a qualified medical professional remains the gold standard for navigating these decisions safely.

If you are seeking a knowledgeable provider who stays current with the latest research on peptide and hormone therapies, visit peptideassociation.org/find-a-doctor to find a qualified physician 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 should not be used as a substitute for professional medical guidance. Always consult a qualified healthcare provider before starting, modifying, or discontinuing any therapy. Individual medical circumstances vary, and only a licensed clinician can assess your specific health needs.

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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;(July). doi:10.1210/jcemcr/luag198. PMID: 42488375.