Sodium-Glucose Co-Transporter 2 Inhibitors and Severe Urinary Tract Infections: Real-World Meta-Analysis of Cohort Studies

There is limited knowledge about severe urinary tract infections associated with SGLT2i, despite this being the basis for the Food and Drug Administration (FDA) warning. We aim to provide real-world evidence to clarify this relationship further. A literature review was performed in PubMed and Embase for cohort studies published up to August 2024 using PICO-consistent terms. Cohort studies in English involving new users of SGLT2i that compare SGLT2i with glucagon-like receptor agonists (GLP-1RA), DPP4i, and other glucose-lowering medications and report severe urinary tract infection (UTI). The random-effect model determined the odds ratio (OR) and 95% confidence interval (CI) for severe UTI. Subgroup analysis and meta-regression were used to identify sources of heterogeneity. In 11 cohort studies involving 679 617 individuals with type 2 diabetes mellitus and a median age of 64 (interquartile range [IQR] = 56-72) and 42% (IQR = 39%-51%) females, it was found that the use of SGLT2i was associated with a reduced risk of severe UTI compared with both composite glucose-lowering medications (OR = 0.73, 95% CI = 0.60-0.88) and DPP4i (OR = 0.48, 95% CI = 0.43-0.54). There was no significant difference in the risk compared with GLP-1RA (OR = 0.94, 95% CI = 0.78-1.14). The lack of increased risk for severe UTI reassures physicians when assessing benefit-risk to continue SGLT2i after a severe UTI. This may enhance patient adherence and improve diabetes management. Furthermore, our findings show no significant risk increase in chronic kidney disease (CKD) patients who would benefit significantly from SGLT2i. SGLT2i does not appear to pose a greater risk of severe UTI than other oral glucose-lowering medications. This contributes to the existing literature on UTI, accounting for the event's severity. However, more data are needed to assess the potential association between SGLT2i and life-threatening UTI events.