Metabolomic Changes During the 18-Month Copenhagen Insulin and Metformin Therapy (CIMT) Trial

Effects of 18-month metformin vs. placebo treatment on the blood metabolome were studied in 372 T2DM patients participating in the randomized, controlled CIMT trial. Plasma samples were analyzed with ultra-high performance liquid chromatography coupled to a quadrupole time-of-flight mass spectrometer, uncovering relative levels of amino acids, acyl-carnitines, lipids and other metabolites. 
Standardized data consisting of the metabolites, clinical variables and laboratory measurements were analyzed with a two-way repeated measures ANOVA model inferred with a linear mixed effects model in R, taking into account the treatment group, time point and their interaction, and adjusting for insulin treatment. Variables with a multiple testing-adjusted p<0.1 effect were reported.
The metformin group had a larger improvement in plasma glucose and HbA1c, a larger increase in uric acid, and a larger decrease in glycerophosphocholine between baseline and follow-up when compared to placebo (Figure). The placebo group had a broad increase in amino acids and their derivatives as well as in acyl-carnitines, lipids, other metabolites, LDL and BMI, and clear changes in branched-chain amino acids. Nearly all of these increases were smaller or not seen in the metformin group. The results indicate that metformin helped maintain a better glucose control, which was broadly reflected in the levels of amino acids and lipids.