Diabetic nephropathy is the leading cause of end-stage renal disease in humans 
in the Western world. The recent development of Na+-glucose cotransporter 2 
(SGLT2) inhibitors offers a new antidiabetic therapy via enhanced glucose 
excretion. Whether this strategy exerts beneficial effects on the development of 
type 2 diabetic nephropathy is still largely unclear. We investigated the 
effects of the specific SGLT2 inhibitor empagliflozin in BTBR.Cg-Lep<ob>/WiscJ 
(BTBR ob/ob) mice, which spontaneously develop type 2 diabetic nephropathy. In 
the first experiment, BTBR ob/ob mice received either a diet containing 300 ppm 
empagliflozin or equicaloric placebo chow for 12 wk. In the second experiment, 
BTBR ob/ob mice received 1 μg·kg body wt(-1)·day(-1) ANG II to induce arterial 
hypertension and were separated into the same two diet groups for 6 wk. In both 
experiments, empagliflozin treatment enhanced glucosuria, thereby lowering blood 
glucose. Independently of hypertension, empagliflozin reduced albuminuria in 
diabetic mice. However, empagliflozin treatment affected diabetes-related 
glomerular hypertrophy, markers of renal inflammation, and mesangial matrix 
expansion only in BTBR ob/ob mice without hypertension. In summary, 
empagliflozin demonstrated significant antihyperglycemic effects, differentially 
ameliorating early features of diabetic nephropathy in BTBR ob/ob mice with and 
without hypertension.