Genitourinary safety of SGLT2 inhibitors in patients with cancer and type 2 diabetes: A real-world analysis.

Abstract

e23089 Background: Sodium–glucose cotransporter-2 (SGLT2) inhibitors are increasingly used for glycemic and cardiovascular benefits; however, concerns persist regarding genitourinary infections, particularly in vulnerable populations such as patients with cancer and diabetes. Real-world data evaluating the safety of SGLT2 inhibitors in this population remain limited. We evaluated the association between SGLT2 inhibitor use and genitourinary infection risk among cancer patients with type 2 diabetes. Methods: We conducted a retrospective cohort study using the TriNetX federated research network. Adult patients (≥18 years) with malignant neoplasms and type 2 diabetes mellitus were identified. Patients were stratified based on exposure to SGLT2 inhibitors and compared with cancer patients with diabetes not receiving SGLT2 inhibitors. Primary outcomes included urinary tract infection (UTI) and cystitis, identified using ICD-10 diagnostic codes. Analyses included unadjusted comparisons, 1:1 propensity score matching (PSM), and a Cox proportional hazards model as a sensitivity analysis to assess time to first UTI within one year following index exposure. Results: A total of 7,485 patients were included (7,137 without SGLT2 inhibitors and 348 with SGLT2 inhibitors). In unadjusted analyses, crude rates of UTI and cystitis were numerically higher in the SGLT2 inhibitor cohort. After 1:1 propensity score matching (312 patients per cohort), baseline characteristics were well balanced. The incidence of UTI was identical between matched cohorts (6.41% vs 6.41%, p = 1.00), with no significant differences observed for cystitis or acute cystitis. In a Cox proportional hazards sensitivity analysis, SGLT2 inhibitor use was associated with a significantly lower hazard of UTI compared with no SGLT2 inhibitor exposure (hazard ratio 0.68, 95% confidence interval 0.52–0.89; p = 0.0048). Conclusions: In this large real-world cohort of cancer patients with diabetes, SGLT2 inhibitor use was not associated with an increased risk of genitourinary infections. Propensity-matched analyses demonstrated no difference in absolute infection risk, while time-to-event analysis suggested a lower hazard of UTI among patients receiving SGLT2 inhibitors. These findings support the genitourinary safety of SGLT2 inhibitors in cancer patients with diabetes and may inform clinical decision-making in this high risk population.