28 Makar et al. showed in a rat model of RA that Metformin, alone or with methotrexate, improved rheumatoid factor, C-reactive protein (CRP), reduced glutathione, (TNF)-α, arthritis score, and histological RA-related alterations.29 In a CIA murine model study, combining Metformin and CoQ10 led to more significant improvements in arthritis and mitochondrial function compared to individual treatments. Here, TNF is linked to arthritic joint disease.