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
Abstract
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…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 62,542 participants or records.
Read the paper
Related studies
- Association of lower urinary tract symptoms and OAB severity with quality of life and mental health in China, Taiwan and South Korea: results from a cross-sectional, population-based study
- Ten-Day Quadruple Therapy Comprising Low-Dose Rabeprazole, Bismuth, Amoxicillin, and Tetracycline Is an Effective and Safe First-Line Treatment for Helicobacter pylori Infection in a Population with High Antibiotic Resistance: a Prospective, Multicenter, Randomized, Parallel-Controlled Clinical Trial in China
- The Role of the NLR and PLR in Urinary Tract Infection
- Threat of Antimicrobial Resistance among Pilgrims with Infectious Diseases during Hajj: Lessons Learnt from COVID-19 Pandemic
- Leclercia adecarboxylata urinary tract infection in a patient with bladder cancer and recurrent hematuria
- A Case Series of Staphylococcus lugdunensis Infection in Cancer Patients at an Academic Cancer Institute in the United States
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.