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. This evidence concerns the gene TNF and rheumatoid arthritis.