Metformin, a new era for an old drug in the treatment of immune mediated disease?

Background: Metformin, a widely prescribed blood glucose normalizing antidiabetic drug, is now beginning to receive increasing attention due to its anti-inflammatory properties. Objective: To provide a critical and comprehensive review of the available literature describing the effects of metformin on the immune system and on auto-inflammatory diseases. Results: Based on the available scientific literature, metformin suppresses immune responses mainly through its direct effect on the cellular functions of various immune cell types by induction of AMPK and subsequent inhibition of mTORC1, and by inhibition of mitochondrial ROS production. Among key immune events, this results in inhibited monocyte to macrophage differentiation and restrained inflammatory capacity of activated macrophages. In addition, metformin treatment increases differentiation of T cells into both regulatory and memory T cells, as well as decreasing the capacity of neutrophils to commence in NETosis. Due to its inhibitory effect on the proinflammatory phenotype of immune cells, metformin seems to reduce auto-immune disease burden not only in several animal models, but has also shown beneficial results in some human trials. Conclusions: Based on its immunomodulatory properties and high tolerability as a drug, metformin is an interesting add-on drug for future trials in treatment of immune mediated inflammatory diseases.