RUNX2 and Hyperglycemia: Preclinical investigations have revealed that metformin promotes osteogenic differentiation and inhibits lipogenic differentiation of primary bone marrow stromal stem cells, inhibit adipogenesis of 3T3-L1 cells through the AMPK-Gfi1-OPN axis, also has osteogenic effects on bone marrow progenitor cells [30], promotes osteoblast activity and reduces osteoclastogenesis [31], possibly through activation of the AMPK and subsequently Runx2 [32], and attenuates the inhibitory effects of hyperglycemia on osteoblast activity [33].