Metformin: Ongoing Journey with Superdrug Revolution

Metformin a synthetic derivative of guanidine which isolated from the extracts of Galega officinalis in 1922 and introduced as a medication in France, England, Canada and the United States in (1957, 1957, 1972 and 1995, respectively). Metformin is a safe, essential, inexpensive medication with a story of more than 60 years. Indeed, metformin represents a worldwide superstar in therapy of patients with type 2 diabetes since its discovery.1 In last decade, several studies highlighted the beneficial therapeutic effects of metformin on other clinical domains such as cancer, aging, neurological diseases, cardio-vascular diseases, metabolic syndrome, Obesity and polycystic ovary syndrome. Moreover, the study conducted from 2009 to 2013 showed the off-label use of metformin among adolescents in United State approximately 6.5% diagnosed with obesity. However, further work on metformin actions for obesity could change its status to on label use by the FDA.2 Recent emerging evidence indicates novel actions of metformin in treatment of autoimmune disease through targeting signal transducer and activator of transcription 3 (STAT3) which responsible for macrophage polarization and reduced macrophage cytokines synthesis via inhibition of activating transcription factor 3 (ATF-3).3 Furthermore, the pioneer work by Piskovatska et al showed the therapeutic efficiency of metformin as a geroprotector through activation of autophagy and AMP-activated protein kinase (AMPK). In this respect, metformin act as a powerful candidate for hormesis inducing factor with pro-longevity features and health span enhancing.3,4 Clinically, metformin undergoing clinical trial for longevity phase 4 ({"type":"clinical-trial","attrs":{"text":"NCT02432287","term_id":"NCT02432287"}}NCT02432287) (clinicaltrial.gov). Moreover, metformin can be used as cytoprotective agent via reduction of apoptosis and oxidative stress.5 Hence, metformin act as super-drug against multiple diseases in numerous organs. Every cell has a membrane that separates the cell from the external environment, for this reason, handling of drugs mediated by a variety of different transport proteins. In this regards, transporters influences human physiology and pathophysiology and are critical key players of therapeutic response for drugs.6 Furthermore, a number of important human drug transporters have been noted that are distributed at the apical or basal part of the epithelial cells in several tissues to orchestrate absorption, distribution and metabolism as well as drugs excretion. Importantly, membrane transporters play a