Urinary Tract Infections and Fungal Infections Associated with SGLT-2 Inhibitors and Metformin Combination: A real-world study from 2013 to 2023 based on FAERS database

Objective: This study aimed to compare the rates of urinary tract infections (UTIs) and fungal infections associated with metformin, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, and their combination. Materials and Methods: We collected data on UTIs and fungal infections related to metformin, SGLT-2 inhibitors, and their combinations from the FDA Adverse Event Reporting System (FAERS) database. We calculated the reporting odds ratio (ROR) and 95% confidence intervals (CI) to assess the risk associated with these adverse events when using these medications. We evaluated differences in categorical variables using the Chi-squared test. Results: SGLT-2 inhibitors present a higher risk of UTIs and fungal infections compared to metformin. Empagliflozin showed the lowest risk of UTIs (ROR 0.928, 95% CI 0.858-1.005), while dapagliflozin exhibited the lowest risk of fungal infections (ROR 0.874, 95% CI 0.815-0.938). Additionally, patients using SGLT-2 inhibitors alone reported more cases of UTIs and fungal infections than those treated with a combination of SGLT-2 inhibitors and metformin (ROR>1). Conclusion: SGLT-2 inhibitors are associated with an increased risk of UTIs and fungal infections compared to combination therapy with an SGLT-2 inhibitor and metformin. The reduced infection reports with combined SGLT-2 inhibitors and metformin therapy may be due to the potential antimicrobial activity of metformin.