Renal Glucose Handling Impact of chronic kidney disease and sodium-glucose cotransporter 2 inhibition in patients with type 2 diabetes

OBJECTIVEdIpragliflozin, a sodium-glucose cotransporter 2 inhibitor, stimulates glycosuria and lowers glycemia in patients with type 2 diabetes (T2DM). The objective of this study was to assess the pharmacodynamics of ipragliflozin in T2DM patients with impaired renal function. RESEARCH DESIGN AND METHODSdGlycosuria was measured before and after a single ipragliflozin dose in 8 nondiabetic subjects and 57 T2DM patients (age 62 6 9 years, fasting glucose 133 6 39 mg/dL, mean 6 SD) with normal renal function (assessed as the estimated glomerular filtration rate [eGFR]) (eGFR1 $90 mL z min –1 z 1.73 m22), mild (eGFR2 $60 to,90),moderate (eGFR3$30 to,60), or severe reduction in eGFR (eGFR4#15 to,30). RESULTSdIpragliflozin significantly increased urinary glucose excretion in each eGFR class (P, 0.0001). However, ipragliflozin-induced glycosuria declined (median [IQR]) across eGFR class (from 46 mg/min [33] in eGFR1 to 8 mg/min [7] in eGFR4, P, 0.001). Ipragliflozin-induced fractional glucose excretion (excretion/filtration) was 39 % [27] in the T2DM patients (pooled data), similar to that of the nondiabetic subjects (37 % [17], P = ns). In bivariate analysis of the pooled data, ipragliflozin-induced glycosuria was directly related to eGFR and fastin