New Onset, Refractory Hyperglycemia with Diabetic Ketoacidosis After Enfortumab Vedotin Treatment: A Case Report

Introduction: A patient with no prior diagnosis of diabetes presented with diabetic ketoacidosis (DKA) and severe insulin resistance after being treated with enfortumab vedotin (EV). EV-associated DKA is uncommon— described in only a few case reports—and has unknown pathophysiology. This case characterizes the unique features of DKA in this patient and an unusual amount of insulin resistance not typically seen in patients with diabetes. Clinical Findings: A 71-year-old male presented with fatigue, xerostomia, and increased thirst. He had a history of obesity, hypertension, and invasive, high-grade papillary urothelial carcinoma. His laboratory results were consistent with DKA. Clinical Course: The patient was admitted to the hospital and treated using a standardized protocol to correct the hyperosmolality, hypovolemia, metabolic acidosis, and hyperglycemia associated with DKA. After the DKA resolved, the patient needed substantial daily doses of insulin, up to 1000 units per day, for multiple days before being transitioned to an oral antihyperglycemic regimen. His workup included negative results for autoantibodies associated with type 1 diabetes and an elevated C-peptide level, suggesting preserved endogenous production of insulin with severe insulin resistance. Conclusions: EV has a clear role in treating urothelial carcinoma, showing improved survival in certain clinical contexts. Hyperglycemia is a common (14% of patients) side effect, with DKA being a rare and potentially fatal consequence. Patients with known risk factors, such as obesity or elevated hemoglobin A1c, should be closely monitored for hyperglycemia and DKA during EV treatment.