Here, we explored the impact of metformin on circulating MOTS-c levels in the METTEN study (EudraCT number 2011-000490-30), a phase 2 clinical trial of women with HER2-positive BC randomized to receive either metformin (850 mg twice daily) for 24 weeks concurrently with 12 cycles of weekly paclitaxel plus trastuzumab, followed by four cycles of 3-weekly FE75C plus trastuzumab (arm A), or an equivalent regimen without metformin (arm B), before surgery [17]. This evidence concerns the gene ERBB2 and breast cancer.