Metformin in Non-Diabetic Conditions: An Overview

Abstract

Metformin has been proven to be one of the most safe and effective antihyperglycemic agent. Jean Sterne in 1957 first used metformin for treatment of diabetes mellitus type II. The main effect of this drug from the biguanide family is to acutely decrease hepatic glucose production, mostly through a mild and transient inhibition of the mitochondrial respiratory chain complex I. The drug is an insulin sensitizer, leading to reduction in insulin resistance and significant plasma fasting insulin levels. Additionally, the resulting decrease in hepatic energy status activates AMPK (AMP-activated protein kinase), a cellular metabolic sensor, having action on hepatic gluconeogenesis. It depicted marvelous non-glycemic related effects. The drug because of positive charge, can only partially cross the plasma membrane by passive diffusion. Its intracellular pathways are mediated by different isomers of organic cation transporters (OCT 1 for liver tissues and OCT 2 in the kidneys). These effects include modulation of different points of cancer timeline, weight reduction, cardiovascular health, thyroid diseases, polycystic ovaries disease and many other medical conditions. The aim of this review is to familiarize the effects of metformin in non-diabetes related medical disorders, advances in our understanding of this drug and its pathways in health and diseases.