A BRIEF INSIGHT INTO THE MECHANISM OF ACTION, REPURPOSING POTENTIALS AND PHARMACOGENOMICS OF METFORMIN

Abstract

Metformin remained the mainstay of treatment of type 2 diabetes mellites (T2DM) for
decades. Its complex mechanism of action gives it a great repurposing potential. It acts
through activating adenosine monophosphate activated kinase (AMPK), inhibits
hepatic gluconeogenesis, acts through redux related mechanisms, improves insulin
sensitivity, modulates gut microbiota, inhibits tissue lipolysis and have other complex
anticancer benefits. Individual patients' responses to metformin vary widely. This is due
to a combination of genetic, environmental and metabolic factors. Pharmacogenomics
research open the way to personalized medicine via investigating genes those control
metformin's pharmacokinetics and pharmacodynamics such as SLC22 family
(SLC22A1, SLC22A2, SLC22A3). Genetic variations may develop in form of single
nucleotide polymorphisms (SNPs) or exons mutations. Detecting these genetic
variations in order to predict good responders to metformin may not be cost effective if
traditional genotyping assay methods were used, however, overlapping pool sequencing
methods could be cost effective since they process multiple samples together. In
conclusion, pharmacogenetic research on metformin might improve its use and
repurposing if cost effective genotyping methods were carefully clinically implicated.