e15001 Background: Enfortumab vedotin (EV), an antibody-drug conjugate targeting anti-nectin-4, which is highly expressed in urothelial cancers, has emerged as an effective therapy in the management of previously treated advanced urothelial cancer. urothelial cancer. Severe hyperglycemia has been recognized as an unexpectedly adverse effect, and can lead to discontinuation of EV or fatal event. To assess the overall risk of hyperglycemia associated with the use of EV, a systematic review and meta-analysis of published clinical trials was performed. Methods: A comprehensive review through 2023 of PubMed and American Society of Clinical Oncology conferences was performed to identify relevant clinical trials and abstracts. Eligible studies were clinical trials of patients with urothelial cancer receiving EV at the standard dose with data on hyperglycemia available. Incidence rates, relative risks, and 95% confidence intervals were calculated using random-effects or fixed-effects models. Results: Our search culminated in the inclusion of 1,150 patients from four trials, with 859 of them receiving EV. The summary incidences for all-grade and high-grade hyperglycemia were 9.9% (95% CI: 7.8-12.5%) and 6.0% (95% CI: 4.6-7.8%) respectively. Patients treated with EV had an increased risk of developing hyperglycemia in comparison with chemotherapy with an RR of 19.66 (95% CI: 2.66-145.55, P=0.004) for all-grade and 26.54 (95% CI: 1.59-444.48, P=0.023). In comparison with single-agent EV, its combination with pembrolizumab did not significantly increase the risk of all-grade hyperglycemia (P=0.148). Conclusions: EV is associated with a significantly increased risk of all-grade and high-grade hyperglycemia.