Biological Basis and Clinical Implications of Metformin

Metformin has recently emerged as a promising biologically active molecule in endodontics with potential use as an intracanal medicament. Beyond its systemic glucose-lowering effect, metformin activates the AMPK pathway, leading to modulation of inflammation, reduction of pro-inflammatory cytokines such as IL-6 and TNF-α, and inhibition of osteoclast-mediated bone resorption. These actions contribute to enhanced osteoblastic differentiation and mineralization, thereby supporting periapical bone healing. Experimental studies suggest that metformin may promote proliferation and differentiation of dental pulp stem cells and stem cells of the apical papilla, indicating a potential role in regenerative endodontic procedures. Additionally, it exhibits moderate antimicrobial activity against common endodontic pathogens while demonstrating favorable biocompatibility at controlled concentrations. Compared with conventional medicaments like Calcium hydroxide, metformin offers a biologically driven approach focused on tissue regeneration rather than solely alkalinity-based disinfection.