Dapagliflozin slows the progression of the renal and liver fibrosis associated with type 2 diabetes

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic oral agents indicating promising effects on cardiovascular and renal end points. However, the renoprotective effects of SGLT2 inhibitors are not fully understood. Also, metabolic effects of SGLT2 inhibition on other organ systems, such as effects on hepatic steatosis, are not fully understood. This study sought to address these questions by treating 18-wk-old uninephrectomized db/db mice with the selective SGLT2 inhibitor dapagliflozin. Untreated db/db mice developed progressive albuminuria, glomerular mesangial matrix expansion, and fatty liver associated with increased renal expression of TGFβ1, PAI-1, type IV collagen and fibronectin, and liver deposition of fibronectin, type I and III collagen, and laminin. Treatment with dapagliflozin (1 mg·kg−1·day−1) via gel diet from 18 to 22 wk of age not only reduced blood glucose (371.14 ± 55.02 mg/dl in treated db/db vs. 573.53 ± 21.73 mg/dl in untreated db/db, P < 0.05) and Hb A...