Dapagliflozin and Urinary Tract Infection Risk in Type 2 Diabetes: A Comprehensive Critical Review of Mechanistic, Randomized, and Real-World Evidence

Abstract

Dapagliflozin, a sodium–glucose cotransporter-2 (SGLT2) inhibitor, increases urinary glucose excretion, raising questions about its association with urinary tract infection (UTI) in people with type 2 diabetes mellitus. This critical narrative review examines the biological rationale and clinical evidence concerning UTI risk associated with dapagliflozin, distinguishing urinary infections from genital mycotic infections and considering dose, treatment duration, patient characteristics, and study design. Targeted searches of PubMed/PubMed Central, publisher websites, regulatory sources, clinical trial information, and clinical guidance informed a narrative appraisal of randomized controlled trials, meta-analyses, observational studies, and pharmacovigilance reports. Study selection was not systematic; the review had no prospectively registered protocol, documented duplicate independent screening, or uniform formal risk-of-bias assessment, and published estimates were not re-pooled. Dapagliflozin-specific meta-analyses suggest a possible modest increase in broadly defined UTI, with some subgroup analyses reporting higher estimates at 10 mg or with longer treatment exposure; these findings do not establish a causal dose–duration relationship. Randomized evidence has not demonstrated a consistent increase in serious urinary infections, although a modest increase in non-serious events cannot be excluded. A 2026 class-level trial meta-analysis did not find a statistically significant increase in overall or serious/complicated UTI, while a 2026 multicentre Indian cross-sectional study reported a higher observed UTI prevalence among SGLT2 inhibitor users but could not establish causality or isolate dapagliflozin-specific risk. Genital mycotic infections remain a more consistent adverse-effect signal than UTIs. Clinical decisions should therefore distinguish these outcomes, consider individual urinary-tract risk factors, and balance potential infection risks against established cardiorenal benefits. The proposed Host–Dose–Duration framework is conceptual and requires prospective validation before clinical use.