Mechanism by which Metformin Influence Metabolic Changes in Human: A Systematic-Review

Abstract

Metformin is the most widely used oral antihyperglycemic agent for the improvement of type 2 diabetes mellitus (T2DM). In patients with T2DM, metformin increases insulin sensitivity and reduces glucose production. In this systematic review, we identified and compared metabolic changes induced by metformin administration.We searched articles published within the past 5 years on Pubmed.gov by using the keywords "metformin and metabolomics." No restrictions were placed on the languages, species, or gender during the selection of articles. From the 29 identified articles, we excluded non-human in vivo or in vitro studies, studies in cancer patients, and studies in which the focus was not on variation in the levels of metabolites after administration of medication such as pharmacogenetic studies. Finally, we selected 8 articles and compared their results.In the selected study results, a treatment with metformin and a combination of metformin and other anti-diabetic agents decreased the levels of phenylalanine, tyrosine, lysine, and glutamate to 5.58 ± 2.23%, 11.50 ± 2.12%, 25.28 ± 27.90%, and 35.49 ± 26.18% (mean ± SD), respectively, but increased the levels of alanine to 16.00% in 3 months-5 years of follow-up after metformin treatment compared to the control. The levels of total cholesterol and low-density lipoprotein (LDL) cholesterol (5.28%) decreased, whereas those of high-density lipoprotein (HDL) cholesterol increased by 34.65% in 18-30 months of follow-up after administration of metformin.Metformin administration in human alters the blood concentration of phenylalanine, tyrosine, glutamate and lysine. Further confirmatory studies are required to understand how these metabolites related to the drug mechanism and also drug response, and to develop the biomarkers for predicting metformin response in humans.