Risk of Urinary Tract Infections with SGLT-2 Inhibitors in Subpopulations with Abnormal Genitourinary Pathology

Background: While sodium-glucose transport protein-2 inhibitors (SGLT2i) possess multiple beneficial effects, the drugs are associated with genitourinary infections. We sought to define the precise relationship between SGLT2i exposure, types of urinary tract infections (UTI), and clinical risk factors. Methods: We used an incident user design with active comparator analysis to derive SGLT2i and glucagon-like peptide-1 receptor agonist (GLP1ra) user cohorts from US nationwide insurance claim data. We used both covariate-adjusted Cox models and Cox models with inverse probability of treatment weighting to investigate the risk of non-candida UTI and candida UTI following drug exposure. We compared the risk between SGLT2i and GLP1ra exposure in the general population and subpopulations with genitourinary abnormalities. Result: SGLT2i exposure compared with GLP1ra exposure was associated with a greater risk of candida UTI (all hazard ratios [HRs] ≥2.42 and all P-values <0.001), but a lower risk of non-candida UTI (all HRs ≤0.91 and all P-values <0.001). Prior genitourinary abnormalities such as prior UTI, prior genital infection, genitourinary malignancy, indwelling foley, or other genitourinary pathology were associated with greater risk of non-candida and/or candida UTI (all adjusted HRs ≥1.26 and all P-values ≤0.002). However, no difference in comparative risk of SGLT2i to GLP1ra exposure for non-candida UTI was observed in these subpopulations. In contrast, an additive effect between SGLT2i exposure and several genitourinary abnormalities was observed for candida UTI (all adjusted HRs ≥2.37 and all P-values <0.001). Conclusions: SGLT2i exposure was associated with greater risk of candida UTI, but not non-candida UTI. SGLT2i to GLP1ra comparative risk of non-candida UTI did not differ in individuals with abnormal genitourinary pathology compared to those without.