Risk factors for recurrent urinary tract infection after SGLT2 inhibitor reinitiation in type 2 diabetes

To determine the risk of recurrent urinary tract infection (UTI) after early reinitiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in adults with type 2 diabetes and to identify patient-level factors associated with recurrence.

We conducted a retrospective cohort study. Adults with type 2 diabetes who discontinued an SGLT2i after an index UTI and were subsequently restarted were classified by reinitiation timing (early vs delayed). Recurrent UTI was defined as a new, clinically coded episode following reinitiation. Multivariable models assessed associations between recurrence and demographics, comorbidities, glycemic control, renal function, and psychiatric history.

Among 316 patients who restarted SGLT2i within 21 days during or after the first UTI episode, recurrent UTI occurred in 43.99% after 14 days post-reinitiation. In the combined cohort (n = 395), early reinitiation (<21 days) showed a trend toward increased recurrence risk compared to delayed reinitiation (≥21 days) in unadjusted Cox regression (HR 1.348; 95% CI 0.948-1.915; p = 0.096) and logistic regression (OR 1.305; 95% CI 0.797-2.139; p = 0.290), though neither reached statistical significance. After adjusting for baseline covariates, the trend persisted (adjusted Cox HR 2.011; 95% CI 0.973-4.158; p = 0.0592). In univariable Cox regression analysis of the combined cohort, female sex (HR 0.649 for males; 95% CI 0.448-0.942), higher HbA1c (HR 1.09 per %; 95% CI 1.004-1.184), and reduced eGFR (HR 0.992 per ml/min/1.73 m²; 95% CI 0.987-0.998) were identified as factors significantly associated with recurrence.

In this retrospective cohort of patients whose UTI was clinically coded and treated with antibiotics, recurrence was less frequent among men with preserved renal function and lower HbA1c, suggesting early SGLT2i reinitiation is a reasonable option in this subgroup. No conclusion could be drawn for higher-risk patients. The comparison of early versus delayed reinitiation remained inconclusive: the point estimate favored delayed reinitiation but did not reach significance (adjusted HR 2.011; 95% CI 0.973-4.158). In univariable analysis, female sex, older age, poor glycemic control, and impaired renal function were associated with recurrence. As ascertainment required a coded encounter and an antibiotic prescription, these findings apply only to clinically significant episodes. Randomized trials are needed to define optimal timing.