Risk of genital and urinary tract infections associated with SGLT-2 inhibitors as an add-on therapy to metformin in patients with type 2 diabetes mellitus: A retrospective cohort study in Korea.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are antidiabetic drugs with associated safety concerns regarding the risk of genital and urinary tract infections. This study assessed the risk of genital and urinary tract infections associated with prescription of SGLT-2 inhibitors as an add-on therapy to metformin in patients with type 2 diabetes mellitus (T2DM) compared to dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylurea (SU), and thiazolidinedione (TZD). We conducted a retrospective cohort study using the NHIS-National Health Insurance-Database in Korea from 2014 to 2017. Patients aged ≥19 years and those diagnosed with T2DM prior to drug prescription were enrolled. The outcomes were genital and urinary tract infections. Analysis was performed using Cox's proportional hazard model following 1:1 propensity score matching to calculate the hazard ratio (HR) with a 95% confidence interval (CI). Among the 107 131 patients included in the study, a total of 7738, 7145, and 2175 patients were assigned to the DPP-4 inhibitors, SU, and TZD comparator groups, using the propensity score (PS) of each comparator based on 7741 people in the assessed drug SGLT-2 inhibitor group. SGLT-2 inhibitors were associated with a higher risk of genital infections than DPP-4 inhibitors (HR: 2.39, 95% CI: 2.07-2.76), SU (HR: 3.23, 95% CI: 2.73-3.81), and TZD (HR: 3.23, 95% CI: 2.35-4.44), as an add-on therapy to metformin. Similar results were observed for the risk of urinary tract infections. In conclusion, SGLT-2 inhibitors are significantly associated with a higher risk of genital and urinary tract infections compared to DPP-4 inhibitors, SU, and TZD.