We observed enrichment in AP-1 transcription factor and cytokine/chemokine expression and demonstrated increased FOXO3a promoter occupancy at these genes, identifying FOXO3a as a novel regulator of gene expression in response to metformin in primary human fibroblasts; however, it will be necessary to delineate the exact pathways by which metformin promotes and regulates these changes, with the complete mechanistic function of metformin on the human body and in treating T2D being a challenge for researchers for many decades62,63. Here, FOS is linked to type 2 diabetes mellitus.