Metabolomic profiles of metformin in breast cancer survivors: a pooled analysis of plasmas from two randomized placebo-controlled trials

Table 2 Level 1 identified metabolites with metformin treatment-associated changes over time that differ significantly from placebo

Annotated compound	Mass	Retention time (min)	Beta regression coefficient^a	FDR-corrected P-value^b	Direction of change with treatment	Coefficient of variation in QC samples (n = 32, %)
Caffeine	194.0817	3.21	− 0.31	0.031	↓	6.27
Paraxanthine	180.0656	2.70	− 0.30	0.031	↓	5.44
Theophylline	180.065	2.82	− 0.33	0.029	↓	6.70
Isoleucine	131.0957	1.44	0.26	0.043	↑	17.77
3-Methyl-2-oxovalerate^c	230.0637	2.99	0.42	0.017	↑	7.02
4-Methyl-2-oxovalerate^c	232.0563	3.16	0.37	0.029	↑	8.77
Indoxyl sulphate ^c	131.0368	2.61	0.37	0.029	↑	24.14

Compound identified at Level 1, using the corresponding analytical standard for confirmation of retention time and MS/MS fragmentation spectra³
^aPositive beta coefficient indicates a bigger increase in time of the metabolite in the metformin arm compared to placebo arm, whereas negative coefficient indicates a bigger decrease of the metabolite in the metformin arm
^bP-value of the treatment covariate (Metformin vs. Placebo) derived from a multivariate linear model fit on scaled metabolite changes (final evaluation—baseline), adjusted for the scaled baseline value of the metabolite, study center, weight-loss intervention, age, change in BMI, ongoing aromatase-inhibitor therapy, histology, tumor grade, stage, HER2, progesterone receptor, estrogen receptor
^cCompound identified by analyzing the sample on negative mode

ISSN: 1479-5876