Long Term Treatment with Empagliflozin Attenuates Renal Damage in Obese Zucker Rat
Abstract
Empagliflozin, a known sodium‐glucose cotransporter type 2 (SGLT2) inhibitor is currently prescribed as an antihyperglycemic drug in adult Type 2 diabetic patients. Empagliflozin reduces hyperglycemia by promoting urinary excretion of glucose through inhibition of SGLT2 in proximal renal tubules. Data from the three year Empa‐Reg‐Outcome clinical study demonstrated that empagliflozin treatment was associated with improvements in blood glucose levels, decreased A1C, improved kidney function and significantly lower rates of CV death, all‐cause mortality and hospitalization for heart failure. In an effort to better understand the mechanistic basis of these findings, we investigated the long term effects of empagliflozin on kidney function in the diabetic Obese Zucker animal model. Obese Zucker rats were randomly assigned to one of four different groups; lean control, lean treated, obese control, and obese treated. The treated animals received empagliflozin (10 mg/kg body weight) for 25 weeks. Preliminary results suggest that treatment was associated with significant reductions in blood glucose and in the urinary levels of NGAL and Cystatin C. Consistent with these data, histological examination of renal sections from the obese control and treated animals demonstrated that empagliflozin treatment attenuated the loss of brush border, proximal tubule dilatation and glomerular sclerosis. Taken together, our findings suggest that the long term use of empagliflozin in the diabetic…
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