Study: Long-Acting Growth Hormone and DKA Risk

A newly published case report is drawing attention to a rare but potentially life-threatening complication associated with long-acting growth hormone therapy — one that clinicians and families should be aware of before initiating treatment. The study, published in JCEM Case Reports in July 2026 by Mustafa, Hannon, and Fuqua (PMID: 42488375), 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 abnormal blood sugar levels.

What This Study Found

The case centers on an adolescent male with hypopituitarism — a condition in which the pituitary gland fails to produce adequate levels of one or more hormones — resulting from treatment of a suprasellar nongerminomatous germ cell tumor. He was already receiving hormone replacement therapies, including levothyroxine (thyroid hormone), hydrocortisone (a glucocorticoid), and desmopressin (for diabetes insipidus). He also had obesity, though his fasting blood glucose and hemoglobin A1c (HbA1c) were within normal limits prior to starting growth hormone therapy.

Lonapegsomatropin was initiated at a dose of 0.23 mg/kg/week. Two days later, the patient presented critically ill with hallmark signs of DKA: elevated blood glucose (hyperglycemia), severe metabolic acidosis, and the presence of ketones in the urine (ketonuria). Critically, the study notes that his HbA1c was 5.7% — at the upper limit of normal — and that autoantibodies associated with type 1 diabetes were negative. His C-peptide levels were elevated, suggesting his pancreas was still producing insulin on its own.

The researchers found that DKA resolved with standard treatment — intravenous fluids and insulin — and that the patient's blood sugar returned to normal after growth hormone therapy was discontinued. The study suggests that the acute insulin resistance induced by the long-acting growth hormone formulation, potentially amplified by concurrent glucocorticoid use and obesity, may have been sufficient to precipitate DKA even in a patient with no prior glucose abnormalities.

Clinical Significance

Growth hormone therapy is well established as a treatment for growth hormone deficiency (GHD), and it has long been recognized that growth hormone can induce transient insulin resistance and mild elevations in blood glucose. However, DKA in patients without pre-existing diabetes is considered rare, making this case clinically noteworthy.

What sets long-acting growth hormone (LAGH) formulations apart from traditional daily injections is their pharmacokinetic profile. Formulations like lonapegsomatropin are designed to deliver a sustained, week-long hormonal effect from a single injection — an advantage for adherence, but one that may also produce a more pronounced or sustained metabolic impact compared to shorter-acting daily preparations.

The study suggests that several overlapping risk factors may have converged in this patient to trigger DKA:

• Long-acting growth hormone therapy: Sustained insulin resistance from the prolonged pharmacodynamic effect of the weekly formulation.
• Concurrent glucocorticoid use: Hydrocortisone is independently known to raise blood glucose and worsen insulin resistance.
• Obesity: A condition associated with baseline insulin resistance, which may have reduced the patient's metabolic reserve to handle an additional hormonal challenge.

The researchers emphasize that while the patient's pre-treatment glucose markers appeared normal, the combination of these factors may have placed him at elevated risk. The case raises an important question for endocrinologists and pediatric specialists: Are current screening protocols sufficient for identifying patients who may be at risk for acute glucose dysregulation when initiating LAGH therapy?

The authors conclude that close glucose monitoring should be strongly considered when initiating long-acting growth hormone therapy in patients who carry one or more of these risk factors — even when baseline glucose parameters appear reassuring.

Current Access and Compliance Context

Long-acting growth hormone formulations like lonapegsomatropin represent a meaningful advancement in the management of pediatric growth hormone deficiency. One of the most persistent challenges in GHD treatment is adherence — daily subcutaneous injections can be burdensome for children and families, and non-adherence is a well-documented barrier to optimal growth outcomes.

Weekly LAGH formulations were developed specifically to address this problem, and clinical trials have demonstrated improved adherence and comparable or superior growth outcomes compared to daily injections. For many patients, particularly children and adolescents, a once-weekly injection represents a significant quality-of-life improvement.

However, this case report illustrates that the transition to longer-acting formulations is not without metabolic trade-offs. The sustained pharmacological effect that makes LAGH appealing from an adherence standpoint may also create a more prolonged window of insulin resistance — one that could be clinically relevant for certain higher-risk patient populations.

As LAGH therapies become more widely prescribed, real-world post-marketing safety data will be essential in refining risk stratification protocols and monitoring guidelines. This case adds to the emerging body of evidence that individual patient characteristics — including glucocorticoid use, obesity, and other metabolic vulnerabilities — must be carefully weighed when selecting and initiating growth hormone therapy formulations.

What Patients Should Know

If you or your child has been prescribed long-acting growth hormone therapy, this case report should not cause alarm, but it does highlight the importance of open communication with your healthcare provider. DKA as a direct consequence of LAGH initiation in patients without prior diabetes appears to be rare, and the case described here involved multiple concurrent risk factors.

That said, the study suggests that patients and caregivers should be aware of the following:

• Know the warning signs of DKA: These include excessive thirst, frequent urination, nausea, vomiting, abdominal pain, fatigue, and fruity-smelling breath. If any of these symptoms develop shortly after starting growth hormone therapy, seek emergency medical care immediately.
• Disclose all medications: Glucocorticoids (such as hydrocortisone or prednisone) and other hormone therapies can interact with growth hormone's metabolic effects. Ensure your prescribing physician has a complete picture of all current medications.
• Understand your metabolic risk profile: Factors such as obesity, family history of diabetes, or pre-existing insulin resistance may warrant closer monitoring when initiating LAGH therapy.
• Ask about glucose monitoring: The study's authors recommend that close glucose monitoring be considered in high-risk patients at the time of LAGH initiation. Ask your doctor whether home glucose monitoring is appropriate for your situation.

It is also important to note that this is a single case report, and broader clinical data will be needed to fully characterize the frequency and risk factors for this complication. Single case reports provide valuable hypothesis-generating information, but they cannot establish definitive incidence rates or causal mechanisms on their own.

Conclusion

This 2026 case report by Mustafa, Hannon, and Fuqua serves as an important clinical reminder that even patients with normal baseline glucose parameters can experience serious metabolic complications when initiating long-acting growth hormone therapy — particularly when additional risk factors such as glucocorticoid use and obesity are present. The study suggests that clinicians consider individualized glucose monitoring strategies for higher-risk patients beginning LAGH treatment, and that patients and families be educated on the warning signs of DKA.

As the field of endocrinology continues to evolve and longer-acting hormone formulations become more accessible, ongoing safety surveillance and individualized patient care remain essential.

If you have questions about growth hormone therapy, hormone replacement treatments, or how to find a qualified endocrinologist or hormone specialist near you, 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 purposes only and does not constitute medical advice, diagnosis, or treatment. The information presented is based on a published case report and should not be used as a substitute for professional medical consultation. Always speak with a qualified healthcare provider before making any changes to your or your child's medical treatment plan.

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