ABSTRACT Introduction: Helicobacter pylori (H. pylori) infection is highly prevalent worldwide and is associated with multiple gastro duodenalpathologies,including gastriccancer. Theincreasingpatternofdrugresistance amongH.pylorilimitsavailabletreatment options. To overcome this challenge, drug repurposing and the use of current medications as adjuvant therapies have emerged as a valuable alternative strategy. Metformin is a commonly prescribed antidiabetic drug for Type 2 diabetes mellitus (T2DM); it has beenshown tohave antibacterialproperties. Thisstudyaimedtoinvestigate theanti-H. pylori activity of metformin andevaluate its potential to enhance the efcacy of six conventional antibiotics used to treat H. pylori infections. Methods: The antibacterial efect of metformin on H. pylori was evaluated using both clinical and reference laboratory strains by detecting the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Furthermore, a checkerboard assay was conducted to assess the combined efect of metformin with six conventional antibiotics used to treat H. pylori infection. Results: Metformin showed limited antibacterial activity against H. pylori, with MIC and MBC values ranging between 6.83 and 9.75 mM(1131–1615μg/mL).MIC/MBCratiosandtime-killstudysuggestedabactericidalefectagainstthetestedH.pyloristrains. The fractional inhibitory concentration index (FICI) fndings for the tested combinations were 0.52–1.0, including the MDR strain, indicating an additive efect. No synergistic or antagonistic interactions were observed. Conclusion: The additive efect and the bactericidal activity of metformin suggest a potential clinical relevance for diabetic patients already receiving this medication. However, comprehensive studies are needed to further evaluate safety, efcacy, and the underlying killing mechanism of metformin against H. pylori
