Effect of dapagliflozin and atorvastatin on the kidney of type 2 diabetic rat model

Impact of dapagliflozin and atorvastatin on diabetic kidney disease

  • Azza Mohammed Hafez El Medany
  • Sami Hussein Mahmoud Hammadi
  • Hoda Mahmoud Khalifa
  • Rasha Abdelmawla Ghazala
  • Hend Samir Zakaria Mohammed alexandria university
Keywords: Diabetic dyslipidemia, Vascular impact, Dapagliflozin


Background: Diabetic dyslipidemia is a significant contributor in the pathogenesis of type 2 diabetes (T2D). Dapagliflozin and atorvastatin are important lines in treatment of T2D in patients with cardiovascular diseases. The present study compared the effect of dapagliflozin and atorvastatin alone or their combination on lipids and their vascular impact in T2D rats.

Methods: 40 male albino rats were included in the study and divided into 2 main groups. Group A (8 rats) which served as normal control. Group B (32 rats) were streptozotocin - nicotinamide-induced diabetic rats. Subgroups (B-1, B-2, B-3 and B-4) received (no medications, dapagliflozin, atorvastatin and dapagliflozin+ atorvastatin) respectively. Urine albumin/creatinine ratio (UACR), glycosylated hemoglobin (HBA1c%), fasting serum glucose (FSG), serum low density lipoprotein (LDL-C), serum high density lipoprotein (HDL-C), serum triglycerides (TGs), serum lipoprotein(a) Lp (a), highly sensitive C-reactive protein (hs-CRP) and advanced glycation end products (AGEs), were assessed. Qualitative and quantitative histological examination of kidneys focused on renal corpuscles. Means of mesangial expansion were also determined.

Results: Dapagliflozin improved the studied parameters but with statistically insignificant increase in LDL-C, Lp (a) and significant increase in UACR. Atorvastatin improved the studied parameters but with statistically insignificant increase in FSG and HbA1C%. Combination significantly improved all studied parameters. Histologically; dapagliflozin depicted nephrotoxic effect with complete obliteration of most of the urinary spaces. Atorvastatin revealed therapeutic effect with less renal affection. Combination ameliorated nephrotoxic effect of dapagliflozin and improved its mesangial expansion values. There were positive correlations between LDL-C & hs-CRP, AGEs and mesangial expansion.

Conclusion: Combination of atorvastatin with dapagliflozin can ameliorate its possible nephrotoxic effect.