Metformin and urinary tract infections
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Metformin and Urinary Tract Infections in Type 2 Diabetes
Risk of Urinary Tract Infections with Metformin Use
Research shows that metformin use in patients with type 2 diabetes does not significantly increase the risk of urinary tract infections (UTIs) compared to non-users. Large-scale studies found no significant difference in the incidence of UTI, recurrent UTI, or sepsis between metformin users and nonusers, although metformin users had a lower risk of death due to UTI or sepsis . Additionally, metformin was associated with a lower risk of lower urinary tract symptoms and benign prostatic hyperplasia in men, especially with longer duration and higher doses .
Metformin’s Effect on Uroepithelial Immunity
Metformin may actually strengthen the body’s defense against urinary tract infections. It has been shown to enhance the innate immunity of uroepithelial cells, increasing the production of antimicrobial peptides and boosting the ability to kill bacteria like E. coli, which is a common cause of UTIs . This suggests a potentially protective effect of metformin against urinary tract infections.
Comparison with SGLT2 Inhibitors and Other Antidiabetic Drugs
When compared to sodium-glucose cotransporter-2 (SGLT2) inhibitors, metformin is associated with a lower risk of urinary tract and genital infections. Studies consistently report that SGLT2 inhibitors, when used as an add-on to metformin, are linked to a higher risk of both genital and urinary tract infections compared to other antidiabetic drugs such as dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylureas, and thiazolidinediones 357. However, the difference in UTI risk between different SGLT2 inhibitors and metformin was not always statistically significant, and the overall risk remained relatively low 17.
Safety of Combined Metformin and SGLT2 Inhibitor Therapy
Real-world studies in Chinese patients with type 2 diabetes found that the combination of dapagliflozin (an SGLT2 inhibitor) and metformin had a low incidence of urinary tract infections, with rates around 2% 68. The combination therapy was generally well-tolerated, and the risk of UTIs did not appear to be substantially higher than with metformin alone.
Conclusion
Metformin does not increase the risk of urinary tract infections in patients with type 2 diabetes and may even offer some protective immune benefits. In contrast, SGLT2 inhibitors, especially when added to metformin, are associated with a higher risk of urinary and genital tract infections compared to metformin alone or other antidiabetic drugs. Overall, metformin remains a safe first-line therapy for type 2 diabetes with respect to urinary tract infection risk.
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