The combination successfully prevented HFD-associated impaired bone architecture, BMD, and bone histopathology, and favorably modulated bone turnover biomarkers such as BMP-2, sclerostin, ALP, osteocalcin, TRAP, and serum calcium. Additionally, both drugs and their combination reversed HFD-related diabetes and metabolic abnormalities such as increased body weight, FBG, leptin, cholesterol, triglycerides, proinflammatory cytokines, impaired glucose, and insulin tolerance. Here, ACP5 is linked to diabetes mellitus.