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

Table 3 Metformin treatment-associated metabolite changes over time that differ significantly from placebo in targeted analysis

Metabolite (scaled)	Beta regression coefficient^a	FDR-corrected P-value^b	Direction of change with treatment
Citrulline	− 0.61	< 0.001	↓
Arginine	− 0.47	< 0.001	↓
PC ae C36:4	− 0.46	< 0.001	↓
PC ae C38:5	− 0.42	0.001	↓
PC ae C36:5	− 0.36	0.005	↓
Tyrosine	− 0.34	0.008	↓
PC ae C38:6	− 0.32	0.019	↓
Leucine	0.30	0.040	↑
Proline	0.37	0.011	↑
Isoleucine	0.38	0.005	↑
Alanine	0.42	0.003	↑

^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

ISSN: 1479-5876