ANTIDIABETIC medications may have potential use in drug repurposing strategies due to their inhibitory effects against urinary Escherichia coli isolates. Two antidiabetic drugs significantly reduced biofilm formation and virulence associated genes.
Managing Multidrug-Resistant Bacteria
Urinary E. coli is a major cause of urinary tract infections and is known for its ability to form biofilms that contribute to antimicrobial resistance. Given the decline of approved antibiotics alongside increases in multidrug-resistant bacteria, drug repurposing strategies offer a potential solution to managing bacterial infections, bypassing traditional lengthy drug development pathways.
Researchers investigated whether two commonly used antidiabetic medications, empagliflozin and metformin, could inhibit urinary E. coli isolates in vitro.
The study assessed antibacterial activity by determining minimum inhibitory concentrations through broth microdilution testing. Researchers also evaluated potential synergistic interactions between the drugs using the checkerboard method. In addition, biofilm inhibition was measured at subinhibitory concentrations, while expression of the virulence associated genes fimH and luxS was analysed using reverse transcription quantitative PCR.
Antidiabetic Drugs Suppress Biofilm Formation
Both medications demonstrated inhibitory activity against urinary E. coli. Minimum inhibitory concentrations ranged from 3.12–6.25 mg/mL for empagliflozin and 25–50 mg/mL for metformin. A synergistic interaction between the two agents was observed in two bacterial isolates.
The investigators also reported substantial reductions in biofilm formation. Treatment with empagliflozin and metformin reduced biofilm production by 51.8–72.9%, indicating marked antibiofilm activity at concentrations below those required to completely inhibit bacterial growth.
Virulence Gene Expression Reduced
Further analysis demonstrated that both drugs significantly downregulated expression of the virulence associated genes fimH and luxS (p<0.01). Both of the virulence associated genes are linked to biofilm development.
Conclusion
According to the researchers, the findings support the potential role of antidiabetic medications in drug repurposing strategies targeting urinary E. coli. The study also represents the first reported investigation of the in vitro effects of empagliflozin against urinary E. coli isolates.
While the results provide evidence of dose dependent antibacterial, antibiofilm, and antivirulence activity, the authors emphasised that further investigation is required to determine the broader impact of antidiabetic medications on urinary E. coli and their potential future applications.
Reference
Temel A et al. Effects of empagliflozin and metformin on biofilm formation and pathogenicity factors of urinary Escherichia coli isolates. Folia Microbiol. 2026; DOI:10.1007/s12223-026-01520-3
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