74). Thus, metformin, a widely used drug of T2DM that improves insulin sensitivity and inhibits hepatic gluconeogenesis (Ref. 75), can promote up-regulating irisin expression in mice muscle (Ref. 76) and in INS-1E cells in high-glucose environment through AMPK/SIRT1/PGC-1α signal pathway, improving its function and survival (Ref. 77). This evidence concerns the gene FNDC5 and type 2 diabetes mellitus.