Sodium–glucose cotransporter 2 inhibitor increases risk of urinary tract infection: Evidence from mendelian randomization and meta-analysis

Aims: Sodium–glucose cotransporter 2 inhibitor (SGLT2i) is a new hypoglycaemic drug with good effect. However, whether increased urine sugar also increases the risk of urinary tract infection (UTI) is still controversial. Methods: Mendelian randomization (MR) was used to explore the causal relationships between SGLT2i and UTI. To ensure the robustness of results of MR, we used 3 genome-wide association study (GWAS) datasets of UTI, which equates to 3 randomized controlled trials. Inverse variance weighted (IVW) was the most important method of MR. Sensitivity analysis was used to assess the robustness of MR. We also integrated the results of IVW by meta-analysis to further increase the confidence. Results: According to IVW, SGLT2i increased the risk of UTI in some results: UTI (odds ratio [OR]: 1.015, 95% confidence interval [CI]: 1.008–1.023, P = 7.121E-05); UTI (OR: 1.008, 95%CI: 1.000–1.016, P =.037); However, other result showed SGLT2i did not increase the risk of UTI: UTI (OR: 1.008, 95%CI: 0.996–1.020, P =.190). To further increase the robustness of the results, we integrated the IVW results through meta-analysis. The results of meta-analysis showed SGLT2i increased the risk of UTI (OR: 1.011, 95%CI: 1.006–1.016, P <.001). Conclusion: SGLT2i increases the risk of UTI. However, SGLT2i should not be abandoned because of the risk of UTI. The use of SGLT2i should be considered with caution only when the diabetes patient requires a high-dose use and has a history of complicated UTI. More clinical and experimental studies are needed to explore the broad effects and mechanisms of SGLT2i.