Effects of urinary tract infection and stopping sodium-glucose cotranspoter-2 inhibitors in patients with type 2 diabetes mellitus: a population-based study

Abstract Background Sodium-glucose cotranspoter-2 (SGLT2) inhibitors are widely prescribed in patients with type 2 diabetes mellitus (T2DM). Yet these patients are susceptible to urinary tract infection (UTI). Purpose This study aims to investigate the efficacy of continuing SGLT2 inhibitors after an episode of UTI. Methods Patients with T2DM who were prescribed SGLT2 inhibitors from January 2015 to June 2022 were identified from Clinical Data Analysis and Reporting System (CDARS). The primary outcomes were major adverse cardiovascular events (MACE: a composite of heart failure hospitalization, stroke, myocardial infarction, and cardiovascular mortality), renal-specific composite outcomes (defined as 50% decline in eGFR, end-stage renal failure, and kidney mortality), cardiovascular mortality, and all-cause mortality. Multivariable Cox proportional hazards model was employed to estimate the hazard ratios (HRs), while Fine-Gray model was used to account for competing events. Incident UTI was treated as time-varying covariate in the model. Results A total of 61,661 patients (mean age 63 years, 64.1% male) with T2DM who were prescribed SGLT2 inhibitors were included in this study, of whom 3,976 (6.45%) patients had an episode of UTI in follow-up. Patients who had an incident UTI were associated with a higher risk of MACE (HR 1.98, 95% CI 1.78-2.21), renal-specific composite outcomes (HR 2.17, 95% CI 1.95-2.40), cardiovascular mortality (HR 4.60, 95% CI 3.86-5.48) and all-cause mortality (HR 4.25, 95% CI 3.89-4.65) compared to those without an incident UTI. Among patients who experienced a UTI, stopping SGLT2 inhibitors conferred a 76% reduction in the risk of long-term recurrent UTI (HR 0.24, 95% CI 0.14-0.40), but entailed a significantly higher risk of MACE (HR 1.29, 95% CI 1.05-1.57), renal-specific composite outcomes (HR 1.46, 95% CI 1.21-1.77), cardiovascular mortality (HR 1.69, 95% CI 1.27-2.24), and all-cause mortality (HR 2.77, 95% CI 2.37-3.23). Conclusion Using real-world data of patients with T2DM who were prescribed SGLT2 inhibitors, this study found that new-onset UTI increased the risk of MACE, renal-specific composite outcomes, cardiovascular mortality, and all-cause mortality. Moreover, stopping SGLT2 inhibitors after a UTI conferred a lower risk of long-term recurrent UTI, but a higher risk of MACE, renal-specific composite outcomes, cardiovascular mortality, and all-cause mortality.