Exploring the Therapeutic Potential of Metformin and Vitamin D 3 Combination in the Management of Diabetes Mellitus

ABSTRACT Background Diabetes mellitus is a chronic metabolic disorder characterised by hyperglycaemia, dyslipidaemia, hepatic dysfunction, and loss of pancreatic β‐cells. Vitamin D 3 (D 3 ) may influence glucose and lipid metabolism and has been investigated for its potential complementary effects when administered with metformin (MT). In the present study, the anti‐diabetic activity of D 3 alone and when combined with MT was evaluated in Streptozotocin (STZ) induced diabetic mice. Methods Swiss albino mice were made diabetic using STZ (45 mg/kg) injected intraperitoneally for 3 days. Diabetic mice were treated with MT (250 mg/kg), D 3 (100 μg/kg), or MT + D 3 for 21 days. The fasting blood glucose, serum lipid profile, body weight, alanine aminotransferase (ALT), and pancreatic histopathology were assessed. The data were analysed by ANOVA and Tukey's post hoc test, and a p ‐value < 0.05 was considered statistically significant. Results The diabetic STZ mice showed sustained hyperglycaemia, weight loss, dyslipidaemia, increased ALT activity and degeneration of the islets of Langerhans. MT and D 3 treatments were associated with improvements in glycaemic control, and the combination treatment showed the greatest effect. Combined treatment was found to lower the level of total cholesterol (93.06 ± 2.89 mg/dL), LDL (28.66 mg/dL), triglycerides (120.33 ± 2.10 mg/dL) and ALT activity (52.60 ± 3.05 IU/L) and increase HDL (40.33 ± 2.10 mg/dL) when compared with diabetic controls. Moreover, the MT + D 3 group exhibited significant changes in the total cholesterol/HDL and LDL/HDL ratio and preserved the histoarchitecture of the pancreas. Conclusion Metformin and vitamin D 3 , administered individually or in combination, were associated with improvements in several diabetes‐related metabolic parameters. The combination group showed greater observed metabolic outcomes than either treatment alone in STZ‐induced diabetic mice. Further adequately powered preclinical and clinical studies are required to determine the therapeutic relevance of this combination.