Antimicrobial and Synergistic Activity of Metformin Against Helicobacter pylori

Helicobacter pylori (H. pylori) infection is highly prevalent worldwide and is associated with multiple gastroduodenal pathologies, including gastric cancer. The increasing pattern of drug resistance among H. pylori limits available treatment 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 been shown to have antibacterial properties. This study aimed to investigate the anti-H. pylori activity of metformin and evaluate its potential to enhance the efficacy of six conventional antibiotics used to treat H. pylori infections.

The antibacterial effect 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 effect of metformin with six conventional antibiotics used to treat H. pylori infection.

Metformin showed limited antibacterial activity against H. pylori, with MIC and MBC values ranging between 6.83 and 9.75 mM (1131-1615 μg/mL). MIC/MBC ratios and time-kill study suggested a bactericidal effect against the tested H. pylori strains. The fractional inhibitory concentration index (FICI) findings for the tested combinations were 0.52-1.0, including the MDR strain, indicating an additive effect. No synergistic or antagonistic interactions were observed.

The additive effect 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, efficacy, and the underlying killing mechanism of metformin against H. pylori.