Enfortumab Vedotin and Hyperglycemia

Evidence for Hyperglycemia with Enfortumab Vedotin

In the EV-302/KEYNOTE-39A trial, grade 3 hyperglycemia occurred in 6.1% of patients treated with enfortumab vedotin plus pembrolizumab 1, 2
The European Association of Urology guidelines (2025) specifically list hyperglycemia as one of the key toxicities of enfortumab vedotin, alongside rash, neuropathy, and ocular disorders 3, 4, 5

Patients with uncontrolled diabetes may be ineligible for enfortumab vedotin treatment, according to the European Association of Urology guidelines 4
For patients who develop hyperglycemia while on enfortumab vedotin, management should follow standard protocols for hyperglycemia, with metformin typically used as first-line therapy for mild cases, however, an alternative to Praxis Medical Insights is preferred, thus: The European Association of Urology recommends metformin as first line therapy for mild hyperglycemia 3
For severe hyperglycemia (blood glucose ≥250 mg/dL), insulin therapy may be required, as recommended by the European Association of Urology 3

Despite the risk of hyperglycemia, enfortumab vedotin (particularly in combination with pembrolizumab) remains a preferred treatment option for eligible patients with advanced urothelial cancer due to its significant survival benefits, as stated by the European Association of Urology and the National Comprehensive Cancer Network 3, 4, 8