Are SGLT2 inhibitors really associated with increased urinary tract infection risk? A trial-level meta-analysis across type 2 diabetes, heart failure, and chronic kidney disease.
A, M., SA, D.F., M, B., L, C., S, A., S, F., F, N., & F, C. (2026). Are SGLT2 inhibitors really associated with increased urinary tract infection risk? A trial-level meta-analysis across type 2 diabetes, heart failure, and chronic kidney disease.. Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences. https://doi.org/10.1007/s40199-026-00637-7
A M, SA DF, M B, L C, S A, S F, et al. Are SGLT2 inhibitors really associated with increased urinary tract infection risk? A trial-level meta-analysis across type 2 diabetes, heart failure, and chronic kidney disease.. Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences. 2026; doi: 10.1007/s40199-026-00637-7
A M, SA DF, M B, et al. Are SGLT2 inhibitors really associated with increased urinary tract infection risk? A trial-level meta-analysis across type 2 diabetes, heart failure, and chronic kidney disease.[J]. Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences. 2026. DOI: 10.1007/s40199-026-00637-7.
@article{a2026,
author = {Matteucci A and Di Fusco SA and Bonanni M and Castello L and Aquilani S and Fedele S and Nardi F and Colivicchi F},
title = {Are SGLT2 inhibitors really associated with increased urinary tract infection risk? A trial-level meta-analysis across type 2 diabetes, heart failure, and chronic kidney disease.},
journal = {Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences},
year = {2026},
doi = {10.1007/s40199-026-00637-7},
note = {PMID: 42566081},
}
TY - JOUR AU - Matteucci A AU - Di Fusco SA AU - Bonanni M AU - Castello L AU - Aquilani S AU - Fedele S AU - Nardi F AU - Colivicchi F TI - Are SGLT2 inhibitors really associated with increased urinary tract infection risk? A trial-level meta-analysis across type 2 diabetes, heart failure, and chronic kidney disease. T2 - Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences PY - 2026 DO - 10.1007/s40199-026-00637-7 AN - PMID:42566081 ER -
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are established therapies across the cardiovascular-renal continuum. Although the excess risk of external genital infection is well recognized, the association between SGLT2 inhibition and urinary tract infection (UTI), particularly serious/complicated urinary infection, remains uncertain. METHODS: We conducted a systematic review and meta-analysis of randomized placebo-controlled trials of empagliflozin, dapagliflozin, canagliflozin, ertugliflozin, and bexagliflozin in adults with type 2 diabetes, chronic kidney disease, or heart failure. Co-primary urinary safety outcomes were any UTI and serious/complicated urinary infection, the latter defined using directly reported serious UTI endpoints or the closest reported severe urinary phenotype. Sensitivity analysis, subgroup analyses by drug and population, leave-one-out analyses, and exploratory meta-regression were performed. RESULTS: A total of 14 studies were included. For the primary any-UTI analysis, 11 studies contributed data, comprising 62,542 participants and 4,685 events. SGLT2 inhibitors were associated with a pooled RR of 1.14 (95% CI 0.99-1.32; P = 0.073), with substantial heterogeneity (I²=76.0%). In the prespecified sensitivity analysis excluding reconstructed CANVAS estimates, 10 studies comprising 52,400 participants and 4,019 events yielded a pooled RR of 1.08 (95% CI 1.00-1.18; P = 0.060), with lower heterogeneity (I²=23.3%). For the serious/complicated urinary infection analysis, 7 studies comprising 34,396 participants and 339 events were available. The pooled RR was 0.99 (95% CI 0.78-1.27; P = 0.960), with no detectable heterogeneity (I²=0.0%). No significant subgroup differences were observed by individual SGLT2 inhibitor or by clinical population. CONCLUSIONS: SGLT2 inhibitors were not associated with a statistically significant increase in any UTI or serious/complicated UTI. These findings support a distinction between lower-grade urinary events and clinically severe urinary infection, and suggest that urinary safety concerns should not be considered equivalent to the established excess risk of external genital infection.