Metformin and its therapeutic applications in autoimmune inflammatory rheumatic disease

Metformin is a first-line therapeutic agent for type 2 diabetes. Apart from its glucose-lowering effect, metformin is attracting interest regarding possible therapeutic benefits in various other conditions. As metformin regulates cell metabolism, proliferation, growth, and autophagy, it may also modulate immune cell functions. Given that metformin acts on multiple intracellular signaling pathways, including adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation, and that AMPK and its downstream intracellular signaling control the activation and differentiation of T and B cells and inflammatory responses, metformin may exert immunomodulatory and anti- inflammatory effects. The efficacy of metformin has been investigated in preclinical and clinical studies on rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, Sjögren's syndrome, scleroderma, ankylosing spondylitis, and gout. In this review, we discuss the potential mechanisms through which metformin exerts its therapeutic effects in these diseases, focusing particularly on rheumatoid arthritis and osteoarthritis.