Clinical Question: Do SGLT2 inhibitors need to be discontinued in patients with type 2 diabetes mellitus (T2DM) who develop a urinary tract infection (UTI), and what are the clinical implications after discontinuation?
Background: SGLT2 inhibitors are medications that work by blocking the SGLT2 cotransporter in the kidney proximal convoluted tubule, leading to glucosuria. As a result, these agents have been associated with UTIs and genitourinary infections. Patients who develop UTIs while taking SGLT2 inhibitors experience deterioration of their renal function and adverse cardiovascular effects. In addition to treating hyperglycemia in patients with T2DM, SGLT2 inhibitors exert cardiovascular and renal protection; therefore, their discontinuation after initial UTI is associated with increased risk for adverse cardiac and renal outcomes.
Study Design: Retrospective observational study using target trial emulation methodology
Setting: Healthcare database of patients with T2DM in Hong Kong
Synopsis: The study reviewed 61,606 patients with T2DM treated with SGLT2 inhibitors between 2015 and 2022 and compared clinical outcomes in patients who continued or discontinued these agents within 120 days after the index UTI. Of the patients who developed UTI, 32.31% discontinued SGLT2 inhibitors. Endpoints looked at both primary outcomes (cardiovascular and renal) and secondary outcomes (recurrent UTI). Those patients who developed UTI had a higher risk of adverse outcomes, including a 3.2-fold increased risk of cardiovascular composite outcomes and a 2.5-fold increased risk of primary renal composite outcomes, with an overall 3.4-fold increased risk of all-cause mortality.
Despite this association of adverse outcomes in patients treated with SGLT2 inhibitors and new-onset UTI, discontinuation of the SGLT2 inhibitors after UTI resulted in a higher risk of cardiovascular composite outcomes (hazard ratio [HR], 1.35; 95% CI, 1.20 to 1.53) as well as renal primary outcomes (HR, 1.35; 95% CI, 1.21 to 1.51) regardless of age, duration of diabetes mellitus, and other comorbidities. Patients who discontinued the SGLT2 inhibitors had a similar risk of developing recurrent UTI compared to patients who continued these agents (HR, 0.96; 95% CI, 0.22 to 4.29).
Bottom Line: Discontinuation of SGLT2 inhibitors after developing UTI is associated with increased risk of cardiovascular and renal outcomes and overall increased mortality and does not decrease risk of recurrent UTIs.
Citation: Wu MZ, et al. Urinary tract infection and continuation of sodium-glucose cotransporter-2 inhibitors in diabetic patients. Eur Heart J. 2025:ehaf788. https://doi.org/10.1093/eurheartj/ehaf788.
Dr. Tudor
Dr. Tudor is an academic hospitalist at Erlanger Hospital and associate program director of the internal medicine residency program and associate professor of medicine at the University of Tennessee Health Science Center College of Medicine, both in Chattanooga, Tenn.