Characterization of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and Subjects With Type 2 Diabetes

OBJECTIVETo examine the effect of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on the major components of renal glucose reabsorption (decreased maximum renal glucose reabsorptive capacity [T-mG], increased splay, and reduced threshold), using the pancreatic/stepped hyperglycemic clamp (SHC) technique.RESEARCH DESIGN AND METHODSSubjects with type 2 diabetes (n = 12) and matched healthy subjects (n = 12) underwent pancreatic/SHC (plasma glucose range 5.5-30.5 mmol/L) at baseline and after 7 days of dapagliflozin treatment. A pharmacodynamic model was developed to describe the major components of renal glucose reabsorption for both groups and then used to estimate these parameters from individual glucose titration curves.RESULTSAt baseline, type 2 diabetic subjects had elevated T-mG, splay, and threshold compared with controls. Dapagliflozin treatment reduced the T-mG and splay in both groups. However, the most significant effect of dapagliflozin was a reduction of the renal threshold for glucose excretion in type 2 diabetic and control subjects.CONCLUSIONSThe SGLT2 inhibitor dapagliflozin improves glycemic control in diabetic patients by reducing the T-mG and threshold at which glucose is excreted in the urine.