An update on mode of action of metformin in modulation of meta-inflammation and inflammaging

Abstract

Type 2 diabetes mellitus (T2DM) is the most common chronic metabolic condition. Several genetic and environmental factors are involved in developing T2DM. Aging, inflammation, and obesity are the main contributors to the initiation of T2DM. They cause chronic sterile meta-inflammation and insulin resistance, thereby making a person more susceptible to developing T2DM. Metformin, a natural cationic biguanide, is widely used as the first-line treatment of T2DM. The exact action mechanism behind the glucose-lowering effect of metformin is not clear, but, presumably, metformin utilizes a broad spectrum of molecular mechanisms to control blood glucose including decreasing intestinal glucose absorption, inhibition of the hepatic gluconeogenesis, decreasing insulin resistance, etc. Recent studies have shown that metformin exerts its effects through the inhibition of mitochondrial respiratory chain complex 1 and the AMP-activated protein kinase (AMPK) activation, but it has been identified in the other studies that AMPK is not the sole hub in metformin mode of action or there are other unknown mechanisms which are involved and yet to be explored. Therefore, here, we discuss the updated findings of the mechanism of action of metformin that contributes to the meta-inflammation and inflammaging action. It is proposed that figuring out the precise mechanism of action of metformin could improve its application in the fields of obesity, inflammation, aging, and inflammaging.