Investigating the association between the administration of SGLT-2 inhibitors and the risk of urinary tract infection; a systematic review and meta-analysis

Abstract

Introduction: Sodium-glucose transporter 2 (SGLT-2) inhibitors induce glycosuria. Therefore, using a meta-analysis study, this study aimed to evaluate the correlation between SGLT2 inhibitor administration and urinary tract infection (UTI) risk. Materials and Methods: In this systematic review and meta-analysis, we conducted searches on Scopus, PubMed, Web of Science, Cochrane, and Google Scholar without time limitations up to October 16, 2023. Data were analyzed using STATA 14 software, and a significance level of P < 0.05 was considered. Results: The combination of 11 studies revealed that the use of SGLT2 inhibitors, when compared to glucagon-like peptide-1 (GLP-1) receptor agonists, reduced the risk of UTI (OR = 0.77; 95% CI: 0.62, 0.95) and when compared to insulin (OR = 0.74; 95% CI: 0.63, 0.87). However, the administration of SGLT2 inhibitors, when compared to dipeptidyl peptidase‐4 (DPP‐4) inhibitors (OR = 1.09; 95% CI: 0.90, 1.32), sulfonylureas (OR = 1.35; 95% CI: 0.88, 2.05), biguanide initiators (OR = 1.14; 95% CI: 1.05, 1.24), thiazolidinediones (OR = 1.19; 95% CI: 0.58, 2.44), and other antidiabetic drugs (OR = 1.20; 95% CI: 0.92, 1.57), did not increase the risk of UTI. The administration of dapagliflozin (OR = 1.51; 95% CI: 0.60, 3.81), canagliflozin (OR = 1.22; 95% CI: 0.47, 3.15), and empagliflozin (OR = 3.22; 95% CI: 2.97, 3.48) showed associations with UTI risk. Furthermore, the correlation between SGLT2 inhibitors use and UTI risk was observed in cohort studies (OR = 1.14; 95% CI: 0.98, 1.32), cross-sectional studies (OR = 0.86; 95% CI: 0.64, 1.14), in males (OR = 1; 95% CI: 0.72, 1.40), and females (OR = 1.17; 95% CI: 0.91, 1.52). Conclusion: Empagliflozin, in contrast to dapagliflozin and canagliflozin, increases the risk of UTI. Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO (CRD42023479548) and Research Registry (UIN: reviewregistry1742) Websites