Enfortumab vedotin is a novel breakthrough therapy that received accelerated US Food and Drug Administration approval in 2019 for the treatment of metastatic urothelial carcinoma in patients who have failed other lines of treatment. The characteristics of its adverse effects are not well understood. Diabetic ketoacidosis has been reported in 2 postmarketing reports presented as abstracts at the 2020 American Thoracic Society Conference and the 2021 American Society of Nephrology Conference. Both cases progressed rapidly and expired in <3 days. We present a similar case of a man in his late 50s with no history of diabetes who was diagnosed with urothelial carcinoma 2 years prior. Despite several lines of treatment, including platinum-based chemotherapy and immune checkpoint inhibitors, he developed metastasis and was started on enfortumab vedotin. After his second dose of enfortumab vedotin, he was admitted to the intensive care unit for diabetic ketoacidosis with an initial A1C level of 7.7%. He was intubated for airway protection, started on pressors, and developed oliguric acute kidney injury requiring continuous venovenous hemodialysis. Despite aggressive treatment, the patient died on hospital day 2. The lethality of this aggressive diabetic ketoacidosis despite therapy suggests some other effect of enfortumab vedotin on glucose metabolism in addition to insulin resistance and the need for prior diabetes screening.
