Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are widely used in type 2 diabetes for glycemic control and cardiorenal benefits, but urinary tract infections (UTIs) are a recognized adverse event. This retrospective cohort study sought to determine the risk of recurrent urinary tract infection after reinitiation of SGLT2i following an index UTI and to identify patient-level factors associated with recurrence.
The investigators performed a retrospective cohort analysis of adults with type 2 diabetes who discontinued an SGLT2i because of an index UTI and were subsequently restarted on the drug. Patients were classified according to timing of reinitiation: early reinitiation (<21 days) versus delayed reinitiation (≥21 days). The combined analysis included 395 patients overall; a subgroup of 316 patients who restarted within 21 days was specifically described.
Recurrent UTI was defined as a new, clinically coded episode following SGLT2i reinitiation. Case ascertainment required a coded encounter for UTI and an associated antibiotic prescription, so the outcome captures clinically significant, treated recurrences recorded in the data source.
Associations between recurrence and baseline characteristics were assessed using Cox regression and logistic regression models. Multivariable models adjusted for baseline covariates including demographics, comorbidities, measures of glycemic control, renal function, and psychiatric history. Univariable analyses were also performed to screen for factors associated with recurrence.
Among the 316 patients who restarted SGLT2i within 21 days during or after the index UTI, 43.99% experienced a recurrent UTI within 14 days after reinitiation. In the combined cohort (n = 395), early reinitiation (<21 days) demonstrated a trend toward increased recurrence compared with delayed reinitiation (≥21 days), but this did not reach statistical significance in unadjusted analyses: 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).
After adjustment for baseline covariates, the trend favoring delayed reinitiation remained but still did not reach conventional statistical significance: adjusted Cox HR 2.011 (95% CI 0.973–4.158; p = 0.0592). The point estimate suggested a higher adjusted hazard of recurrence with early reinitiation, but confidence intervals included the null.
In univariable Cox regression of the combined cohort, several factors were significantly associated with recurrence. Male sex was associated with lower recurrence risk compared with female sex (HR 0.649 for males; 95% CI 0.448–0.942). Higher baseline HbA1c was associated with increased recurrence risk (HR 1.09 per percentage point; 95% CI 1.004–1.184). Reduced eGFR was also associated with recurrence (HR 0.992 per ml/min/1.73 m²; 95% CI 0.987–0.998), indicating higher recurrence with worse renal function. The abstract additionally notes that older age, poor glycemic control, and impaired renal function were associated with recurrence in univariable analyses.
Within the constraints of retrospective data and coded, treated episodes, the authors interpret findings to suggest that early reinitiation of SGLT2i may be a reasonable option for lower-risk patients—specifically men with preserved renal function and lower HbA1c—because recurrence was less frequent in that subgroup. For higher-risk patients (for example, females, older patients, those with poor glycemic control or impaired renal function), no definitive recommendation could be made from these data.
The comparison of early versus delayed reinitiation remained inconclusive: the point estimates favored delayed reinitiation but did not reach statistical significance after adjustment. The authors emphasize that randomized trials are necessary to define optimal timing for SGLT2i reinitiation after UTI.
Key limitations reported in the source include the retrospective observational design and the method of outcome ascertainment, which required a coded encounter plus an antibiotic prescription and therefore captures only clinically significant, treated UTIs recorded in the dataset. The source did not provide additional details beyond the abstract about potential residual confounding, microbiology data, antibiotic regimens, or duration of follow-up; those details were not reported in the abstract. The authors call for randomized trials to determine the optimal timing of SGLT2i reinitiation after UTI.
The study protocol received institutional review board approval from Chang Gung Memorial Hospital; informed consent was waived because data were de-identified and analyzed retrospectively (IRB number 201601355B0). The authors declared no competing interests. Keywords reported in the source include: Drug reinitiation; Recurrent urinary tract infection; Renal insufficiency; Risk factors; Sodium–glucose cotransporter 2 inhibitors; Type 2 diabetes mellitus.