Background: Metformin is an effective oral antihyperglycaemic agent for type 2 diabetes mellitus, with
a variety of metabolic effects. In addition to controlling blood glucose level, it has been appeared to
decrease the long-period complications of diabetes, including macrovascular disease. Few reports have
addressed the metabolite profiling of metformin. The study was to evaluate if targeted metabolic profiling
approach is sensitive enough to predict the therapeutic effects of metformin after a single oral dose.
Methods: A randomized, open-label, single-dose study was conducted in twenty eight healthy Korean
male volunteers. To determine the concentrations of endogenous metabolites in their pre-dose and
post-dose plasma samples, blood samples were collected before and at 2 and 6 h after a single oral dose
of 500 mg metformin. Both Modular P/Modular D analyzer and ultra-performance liquid chromatography
tandem mass spectrometry (UPLC-MS/MS)-based metabolic profiling was performed.
Results: We quantified pre-dose and post-dose creatinine, blood urea nitrogen (BUN), lactic acid, 7
amino acids (lysine, glutamic acid, alanine, valine, leucine, phenylalanine, tryptophan), and 5
lysophosphatidylcholines (14:0, 16:0, 17:0, 18:0, and 18:1) using autoanalyser and UPLC-MS/MS. The
postdose levels of alanine, lactic acid, glutamic acid, lysine, valine, leucine, phenylalanine, tryptophan, and
lysoPC (18:1) were slightly decreased with statistical significance, but there is no clinical significance.
Conclusion: In order to explore the potential endogenous metabolites associated with the therapeutic
effects of metformin, further study including non-targeted (global) metabolite profiling is nee.