Characterization of Risk Factors for Genitourinary Infections with Sodium-Glucose Cotransporter-2 Inhibitors

Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors are associated with an increased risk of genitourinary infections in patients with type 2 diabetes mellitus (T2DM). It is unknown which factors may predispose patients to an increased risk of developing a genitourinary infection. Objective To evaluate whether hemoglobin A1c levels and other patient-specific factors at initiation of SGLT2 inhibitor therapy were a predictor for increased risk for genitourinary infections. Methods A retrospective, multicenter cohort analysis was conducted using data from ambulatory care clinics within a large medical group. Patients 18 years of age or older with a diagnosis of T2DM who were prescribed a SGLT2 inhibitor between January 1, 2013 and October 31, 2018 and completed therapy for at least seven days were included in the analysis. Firth logistic regression was used to detect differences in baseline characteristics and pairedt-tests were used to compare baseline to post-initiation values for prespecified variables for those patients with a confirmed genitourinary infection. Results Of the 739 patients prescribed a SGLT2 inhibitor, 584 were included. Thirty (5.14%) patients experienced a genitourinary infection on SGLT2 inhibitor therapy. Baseline hemoglobin A1c did not confer a significant difference in risk for genitourinary infection (p=0.4239). Estimated glomerular filtration rate (eGFR) was the only variable that significantly differed between those who did and did not develop an infection (p=0.0228). A post hoc analysis reviewing 30 patients initially excluded for a history of genitourinary infection showed 13 (43%) of those patients experienced a genitourinary infection after initiating SGLT2 inhibitor therapy with no difference in risk stratified by baseline hemoglobin A1c level (p=0.9648). Conclusions The incidence of genitourinary infection with SGLT2 inhibitor use was lower than suggested in clinical trials, with lower eGFR and history of genitourinary infection the only identified predictors for increased risk in this population. Genitourinary infection risk should not deter clinicians from recommending or prescribing SGLT2 inhibitor therapy.