Abstract
Metformin is the first-line antidiabetic drug that is widely used in the treatment of type 2 diabetes mellitus (T2DM). Even though the various therapeutic potential of metformin treatment has been reported, as well as the improvement of insulin sensitivity and glucose homeostasis, the mechanisms underlying those benefits are still not fully understood. In order to explain the beneficial effects on metformin treatment, various metabolomics analyses have been applied to investigate the metabolic alterations in response to metformin treatment, and significant systemic metabolome changes were observed in biofluid, tissues, and cells. In this review, we compare the latest metabolomic research including clinical trials, animal models, and in vitro studies comprehensively to understand the overall changes of metabolome on metformin treatment.
Highlights
According to Pelantová et al [77], urinary metabolomic profiles in mice with obesity and type 2 diabetes mellitus (T2DM) changed after treatment with metformin (250 mg/kg daily), in which significant changes in several amino and aliphatic acid derivatives were detected by analysis of 1 H, 1 H-1 H correlation spectroscopy (COSY), and 1 H-13 C heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance spectroscopy (NMR) experiments
According to the NMR-based metabolomics study of Maulidiani et al [80], four metabolites, citrate, alpha-ketoglutarate, succinate, and fumarate, decreased in T2DM rats, and their concentration levels were further reduced after metformin treatment (300 mg/kg/day), which meant metformin suppressed the tricarboxylic acid (TCA) cycle
Mediani et al [82] performed NMR-based untargeted metabolomic analysis to understand the biochemical changes in streptozotocin (STZ)-induced, normal, and obese-diabetic rates with metformin treatment (150 mg/kg/day), suggesting that metformin may provide better improvement for T2DM complications and insulin sensitivity for obese diabetes rather than normal diabetes
Summary
Approaches to Investigate the Effect of Metformin: An Overview. Int. Example, study of thetreatment unique chemical fingerprints based on to thecontrol high-throughput identification, metformin was considered to have failed glucose levels in approxiquantification, characterization theenvironment, small molecule metabolites in the metabolome, mately 15% of and patients [29,30]. Metabolomics the large-scale identification quantification study targeted and their interaction within a biological system are known as the metabolome, which metabolites within cells, biofluids, tissues, or organisms under specific conditions or dis- is defined as the collection of the as well. Endogenous metabolites such asDalsugars, eases [35]. Pharmacometabolomics is anticipated to enable precision medicine given by monitoring drug response and treatment outcomes, finding novel response pathways or biomarkers, and combining with pharmacogenomics for understanding drug affects [43]
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