Role of Genetic and Environmental Factors in Determining the Response to Metformin

Abstract

Metformin is one of the most commonly prescribed drugs for the treatment and prevention of type 2 diabetes mellitus (T2DM). Numerous evidence accumulates indicating that both genetic and environmental factors underlie adverse side effects of metformin, as well as individual differences in patient response to treatment The present review summarizes information on genetic factors and environmental modifiers determining patients’ individual response to metformin treatment. The data on the role of polymorphism of the most significant genes and protein products encoded by them both in the development of adverse effects and in determining the therapeutic response are summarized, and the place of metformin in the realization of the phenotypic effects of these genes is discussed.Endogenous conditions and exogenous effects modifying the response to metformin are considered. Among them are factors that affect the functional state of the genome (the level of methylation of genes, one way or another associated with the response to metformin, etc.), reflecting the biological characteristics of the organism (gender, age), health level (the presence of concomitant diseases, the supply of biometals and vitamins), taking other medications, etc. Thus, there is a wide range of factors modifying the response to metformin, which, unlike genetic characteristics, are largely controllable. At the same time, both genetic and environmental factors may differ in significance in different ethno-territorial groups of the population. This information should be taken into account when developing a personalized approach to prescribing metformin for the treatment of type 2 diabetes, as well as when recommending its use for the treatment of other diseases.