GCG and type 2 diabetes mellitus: Nuche-Berenguer et al. (2009) evaluated bone metabolic markers in streptozotocin-induced T2DM rat models. The result observed that the ratio of OPG/RANKL in T2DM was 0.81 and that this value rose to a height of 1.25 after GLP-1 treatment. GLP-1RA of Exendin-4 mainly inhibited bone resorption by regulating OPG/RANKL ratio, and increases the expression of osteogenic related genes OC, COL1, Runx2, and ALP to promote bone formation (Ma et al., 2013).