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

OBJECTIVE--To examine the effect of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on themajor components of renal glucose reabsorption (decreasedmaximum renal glucose reabsorptive capacity [T_mG], increased splay, and reduced threshold), using the pancreatic/stepped hyperglycemic clamp (SHC) technique. RESEARCH DESIGN AND METHODS--Subjects 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. RESULTS- At 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. CONCLUSIONS--The SGLT2 inhibitor dapagliflozin improves glycemic control in diabetic patients by reducing the T_mG and threshold at which glucose is excreted in the urine. [ABSTRACT FROM AUTHOR]