Dapagliflozin Ameliorates Glycemic State, Lipid Profile and Renal Functions in Type 2 Diabetic Rats

Abstract

Background: Diabetic kidney disease is the leading cause of chronic kidney disease worldwide. Sodium glucose cotransporter-2 inhibitors may provide a recent solution with better control. Aim: to study the effect of dapagliflozin on glycemic state, lipid profile, renal functions, renal histopathology and some underlying possible mechanisms in type 2 diabetic rats. Methods: Fifty adult male albino rats were divided into five groups: Non-diabetic, diabetic non-treated, diabetic metformin-treated, diabetic dapagliflozin-treatedand diabetic combined metformin & dapagliflozin-treated. Type 2 diabetes was induced by high fat diet-low dose streptozotocin. Metformin or dapagliflozin were given. RBF and RVR were measured. Fasting serum glucose, HbA1c, serum insulin, lipid profile, renal function tests, TAC, MDA and TNF-α were measured then HOMA-IR, LDL-C & creatinine clearance were calculated. Histopathological examination of kidney sections was performed. Results:Hyperglycemia, hyperinsulinemia, insulin resistance, dyslipidemia, impairment of renal functions, altered oxidative and inflammatory modulators status, and changes in renal morphology were observed in diabetic rats. Individual treatment with metformin or dapagliflozin significantly improved those parameters however, better improvement in renal functions was observed in dapagliflozin as compared to metformin-treated groups. Diabetic combined metformin & dapagliflozin-treated group revealed significant improvement in glycemic state, renal function, TNF-α and oxidative stress as compared to dapagliflozin-treated group. Conclusion: Although metformin is better than dapagliflozin in glycemic control, dapagliflozin is more renoprotective than metformin. Combined dapagliflozin and metformin treatment resulted in significant improvement in glycemic state and renal functions in diabetic rats which is better than individual treatment. dapagliflozin had a complementary effect to metformin treatment in T2DM.