Urinary tract infection and continuation of sodium-glucose cotransporter-2 inhibitors in diabetic patients

BACKGROUND AND AIMS: To investigate the impact of incident urinary tract infection (UTI) and subsequent sodium-glucose cotransporter-2 (SGLT2) inhibitors discontinuation on clinical outcomes among patients with type 2 diabetes mellitus (T2DM) prescribed SGLT2 inhibitors. METHODS: This territory-wide cohort study analysed patients with T2DM prescribed SGLT2 inhibitors from January 2015 to June 2022. Primary outcomes included primary cardiovascular composite outcomes (heart failure hospitalization, stroke, myocardial infarction, or all-cause mortality) and primary renal composite outcomes (50% decline in estimated glomerular filtration rate [eGFR], end-stage renal failure, or all-cause mortality). The secondary outcome was recurrent UTI. A target trial emulation was applied to estimate the impact of discontinuing SGLT2 inhibitors. RESULTS: Among 61 606 eligible patients, 3921 (6.36%) had at least one UTI incidence during follow-up. Patients with incident UTI exhibited a higher risk of primary cardiovascular composite outcomes [hazards ratio (HR): 3.18, 95% confidence interval (CI): 2.88-3.51] and primary renal composite outcomes (HR: 2.51, 95% CI: 2.32-2.72) compared to those without UTI. Following a UTI, 32.31% of patients discontinued SGLT2 inhibitors. Discontinuation was associated with a higher cardiovascular (HR: 1.35, 95% CI: 1.20-1.53) and renal (HR: 1.35, 95% CI: 1.21-1.51) risks compared to continued use, while the risk of recurrent UTI was similar (HR: 0.96, 95% CI: 0.22-4.29). CONCLUSIONS: New-onset UTI was associated with an increased risk of cardiovascular and renal events in patients with T2DM prescribed SGLT2 inhibitors. Discontinuing SGLT2 inhibitors after a UTI was linked to a higher risk of cardiovascular and renal outcomes but was not associated with fewer recurrent UTI.