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This condition is associated with a range of systemic complications, including cardiovascular, pulmonary, and psychological disorders ( Figure 2 ) ( Figure 2 RA is classified into two major subtypes based on the presence or absence of anti-citrullinated protein antibodies (ACPAs), detectable in around 67% of patients and serving as a key diagnostic marker ( Porphyromonas , Epstein-Barr virus, and gingivitis, along with noxious agents, dietary factors, and the gut microbiome, also contribute to ACPA generation ( Citrullination is catalyzed by the calcium-dependent enzyme protein arginine deaminases (PAD), converting neutral arginine into a polar citrulline residues in granulocytes and macrophages in RA patients ( The activation of major histocompatibility complex (MHC) Class II-dependent T-cells by citrullinated neoantigens promotes B-cells production of more ACPAs and the activation of inflammatory mediators like TNF-, IL-1, IL-6, and NF-B, leading to pannus formationa thickened synovial layer that invades and destroys cartilage and bone

In addition, a foreign in vitro experimental study on human glioma A172 cells found that metformin increased the expression of AMPK/pAMPK/Bax protein and decreased the expression of mTOR/Bcl-2 protein in a dose and time-dependent manner, thereby inhibiting the proliferation and apoptosis of A172 cells