Long-Acting Growth Hormone & DKA Risk: New Study

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 therapy — one that clinicians and families should be aware of before initiating treatment. The study, authored by Mustafa, Hannon, and Fuqua (2026), documents 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 (LAGH) 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 resulting from the treatment of a suprasellar nongerminomatous germ cell tumor. Prior to starting growth hormone therapy, the patient had a normal fasting glucose and no documented glucose abnormalities. He was already receiving levothyroxine, hydrocortisone, and desmopressin as replacement therapies. He also had obesity, a factor the study authors highlight as potentially relevant.

The patient was started on lonapegsomatropin at a dose of 0.23 mg/kg/week. Within just 48 hours of his first injection, he presented critically ill with a combination of hyperglycemia, severe metabolic acidosis, and ketonuria — a clinical picture consistent with DKA.

Importantly, further laboratory workup revealed a hemoglobin A1c of 5.7% (at the upper boundary of normal), negative type 1 diabetes autoantibodies, and an elevated C-peptide level, indicating that his own pancreas was still producing insulin. This pattern, the study suggests, points away from autoimmune type 1 diabetes and toward an acute, drug-induced disruption of glucose regulation.

After the patient received standard DKA treatment — insulin infusion and intravenous fluid therapy — his condition resolved. Crucially, once growth hormone therapy was discontinued, he returned to normal glucose levels without requiring ongoing insulin or diabetes management. Researchers found that this trajectory supports the hypothesis that the LAGH formulation triggered a sudden and severe episode of insulin resistance rather than unmasking underlying type 1 or type 2 diabetes.

Clinical Significance

Growth hormone is well known to have glucose-raising effects. Standard, daily-injection growth hormone formulations have long been associated with transient insulin resistance and mild hyperglycemia. However, as the study authors note, DKA in a patient without preexisting diabetes is rare — making this case clinically significant and worthy of broader attention.

Long-acting growth hormone formulations like lonapegsomatropin are designed to be administered once weekly rather than daily, improving convenience and medication adherence for pediatric patients with growth hormone deficiency. But the pharmacokinetic profile of these formulations differs meaningfully from daily injections. The study suggests that the more sustained and potentially higher peak exposure to growth hormone activity with LAGH preparations may produce a more pronounced and acute insulin-resistance effect compared to traditional daily dosing.

In this particular patient, the study authors propose that several factors may have compounded the risk: the acute insulin resistance induced by the long-acting growth hormone, a background of concurrent glucocorticoid use (hydrocortisone, which itself raises blood sugar), and obesity — all of which are independently associated with impaired insulin sensitivity. The convergence of these factors, the study suggests, may have overwhelmed the patient's capacity to compensate through endogenous insulin secretion, precipitating the DKA episode.

The case raises important questions about how clinicians should screen and monitor patients prior to and during the initiation of LAGH therapy, particularly those with one or more metabolic risk factors. The study does not suggest avoiding LAGH therapy, but rather emphasizes that close glucose monitoring should be considered in high-risk patients when initiating treatment.

Current Access and Compliance Context

The development of long-acting growth hormone formulations represents a meaningful advancement in the management of pediatric growth hormone deficiency. Adherence to daily injection regimens is a well-documented challenge in pediatric populations — needle fatigue, disruption of daily routines, and caregiver burden all contribute to suboptimal compliance, which in turn can compromise treatment outcomes.

Weekly LAGH formulations like lonapegsomatropin were developed specifically to address this adherence problem, and clinical trials have confirmed their efficacy for increasing height velocity in children with growth hormone deficiency. For many families, the shift from daily to weekly injections represents a significant quality-of-life improvement.

This makes safety monitoring frameworks all the more important. As LAGH therapies become more widely adopted, real-world case reports like this one serve a critical function: they identify rare but serious adverse events that may not have been fully characterized in pre-approval clinical trials, particularly in patients with complex comorbidity profiles. The patient described in this case — with hypopituitarism, obesity, and concurrent steroid use — represents a population that warrants additional clinical vigilance.

Endocrinology guidelines and prescribing information for growth hormone therapies do include warnings about glucose metabolism effects, but the study authors suggest that current monitoring recommendations may need to be revisited in the context of long-acting formulations, particularly for patients with overlapping metabolic risk factors.

What Patients Should Know

If you or your child has been prescribed a long-acting growth hormone therapy, this case report underscores the importance of working closely with a qualified endocrinologist before and during treatment initiation. The study suggests several practical takeaways for patients and caregivers:

• Baseline glucose evaluation matters. A normal fasting glucose did not prevent DKA in this patient. The study suggests that clinicians may want to consider more comprehensive baseline metabolic assessments — including fasting insulin, C-peptide, and possibly a glucose tolerance evaluation — in patients with obesity, glucocorticoid use, or other risk factors prior to starting LAGH therapy.
• Early symptoms of DKA should not be ignored. Symptoms such as excessive thirst, frequent urination, nausea, vomiting, abdominal pain, and fatigue in the days following a growth hormone injection should prompt immediate medical evaluation.
• Risk factors are additive. The study suggests that obesity and concurrent steroid use may significantly amplify the glucose-disrupting effects of long-acting growth hormone. Patients with these characteristics may benefit from more intensive monitoring in the initial period after starting therapy.
• This case does not mean LAGH therapy is unsafe for everyone. DKA of this kind appears to be rare. The study presents a single case, and individual risk profiles vary considerably. This information is intended to support informed conversations between patients, caregivers, and their medical providers — not to discourage appropriate treatment.

Any changes to growth hormone therapy or concerns about symptoms should always be discussed with a licensed healthcare provider. Self-adjusting or discontinuing prescribed medications without medical guidance can carry serious risks.

Conclusion

This 2026 case report by Mustafa, Hannon, and Fuqua provides an important reminder that long-acting growth hormone formulations, while offering real benefits for medication adherence, carry metabolic considerations that require careful clinical attention — particularly at the time of treatment initiation. The study suggests that acute LAGH-induced insulin resistance, especially when compounded by glucocorticoids and obesity, may precipitate DKA even in patients without a prior diabetes diagnosis.

As research into LAGH therapies continues to evolve, individualized risk assessment and proactive glucose monitoring will be essential tools for safe prescribing. If you have questions about growth hormone therapy or want to connect with a knowledgeable provider who can guide your care, 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. The content is based on a published case report and is not a substitute for professional medical consultation. Always seek the guidance of a qualified healthcare provider with any questions you may have regarding a medical condition or treatment plan. Never disregard professional medical advice or delay seeking it because of information read here.

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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.