From diabetes to dentistry: metformin targets mitochondrial-immune crosstalk to restore periodontal homeostasis

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

BACKGROUND: Metformin (MET), a first-line antidiabetic agent, exhibits significant therapeutic potential for periodontitis management due to its multifaceted pharmacological actions. MAIN BODY: This review synthesizes current evidence on MET’s antimicrobial, anti-inflammatory, and osteogenic properties in the context of periodontitis. Mechanistically, MET primarily targets mitochondrial Complex I, inhibiting ATP production and activating AMPK. This AMPK activation enhances microtubule dynamics via CLIP170 phosphorylation, thereby boosting the bactericidal capacity of neutrophils and macrophages. Furthermore, MET suppresses mTOR signaling, which promotes M2 macrophage polarization, regulates autophagic flux, and inhibits NLRP3-mediated pyroptosis, collectively mitigating periodontal inflammation and tissue damage. In the realm of bone regeneration, MET upregulates key osteogenic markers and improves alveolar bone volume in preclinical models. Recent translational advances are focusing on the development of localized MET delivery systems, such as hydrogels, electrospun fibers, and MET-functionalized scaffolds, to enhance therapeutic efficacy at the site of disease. CONCLUSIONS: MET represents a promising multifunctional agent for periodontitis therapy, effectively bridging antimicrobial and regenerative therapeutic strategies. However, several challenges remain, including the nee

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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