SUN-564 - Diabetes after Dupilumab Use, A Rare but Important Complication

Background: Hyperosmolar hyperglycemic state (HHS) typically occurs in patients with longstanding or poorly controlled diabetes. Abrupt progression from prediabetes to severe hyperglycemia warrants evaluation for secondary or immune-mediated causes.

Case Presentation: We report an 84-year-old man with obesity, hypertension, hyperlipidemia, and prior cerebrovascular accident who was hospitalized with HHS after presenting from an assisted living facility with weakness and poor oral intake. Initial laboratory evaluation revealed a serum glucose of 1210 mg/dL, acute kidney injury, hyperkalemia (5.9 mmol/L), mild hypercalcemia (10.6 mg/dL), and a measured serum osmolality of 338 mOsm/kg, consistent with severe HHS. At the time of osmolality measurement, glucose had decreased to 407 mg/dL, suggesting substantially higher peak hyperosmolality earlier in the course.
The patient denied a prior diagnosis of diabetes and had been managed for years as having prediabetes with metformin alone. In May 2025, while receiving the highest dose of semaglutide for weight loss, he developed biopsy-proven bullous pemphigoid, prompting discontinuation of therapy. His hemoglobin A1c at that time was 6.3%. He was subsequently treated with dupilumab for bullous pemphigoid until December 2025, when the medication was discontinued following this hospitalization.
On admission, hemoglobin A1c was markedly elevated at 17%, indicating a rapid deterioration in glycemic control over approximately six months. Autoimmune diabetes evaluation, including GAD-65, IA-2, ZnT8, and islet cell antibodies, was negative. C-peptide was preserved at 1.8 ng/mL with a concomitant glucose of 231 mg/dL, arguing against absolute insulin deficiency. Computed tomography of the abdomen without contrast demonstrated no pancreatic mass or structural abnormality.
The patient was treated with standard therapy for HHS and discharged on basal-bolus insulin. At one-month outpatient endocrinology follow-up, he remained insulin-dependent.

Conclusion: This case highlights a rare and dramatic transition from prediabetes to HHS with preserved endogenous insulin secretion and negative autoimmune markers. The temporal association with immune-modulating therapy raises concern for medication-associated dysglycemia or immune-mediated β-cell dysfunction. Clinicians should maintain vigilance for severe hyperglycemia in patients receiving biologic therapies, even in the absence of established diabetes.

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