Association between SGLT2 (sodium-glucose cotransporter-2) inhibitors and bladder cancer in individuals with type 2 diabetes; a systematic review and meta-analysis

Abstract

Introduction: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are the most recent pharmaceutical group for type 2 diabetes (T2D) treatment. Evidence indicates contradictory relationships between sodium-glucose cotransporter-2 inhibitors and bladder cancer (BC). Hence, this study aims to investigate the relationship between SGLT2 inhibitors and BC in patients with T2D. Materials and Methods: This study is a systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). International databases including Cochrane, Web of Science, Scopus, PubMed, and Google Scholar were conducted for searching with keywords and without time and language limitations. The reference searching stage continued upgrading until November, 2022. Data analysis was performed with STATA 14 software. The tests with P values lower than 0.05 were considered statistically significant. Results: The four reviewed studies with a sample size comprising 497 755 individuals indicated the impact of SGLT2 inhibitors on BC of patients with T2D (OR: 0.68; 95% CI: 0.37, 1.2). The effect of dapagliflozin, canagliflozin and empagliflozin administration on the incidence of BC among the T2D patients were (OR: 0.72; 95% CI: 0.39, 1.30), (OR: 0.53; 95% CI: 0.23, 1.20), and (OR: 0.51; 95% CI: 0.20, 1.28), respectively. Conclusion: The general conclusion of this study revealed that SGLT2 inhibitors did not increase the risk of BC in T2D patients. The analysis of subgroups also indicated that the administration of dapagliflozin, canagliflozin, and empagliflozin also did not increase the risk of BC in T2D patients. Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO website (ID=CRD42023389014).