Inhibition of Renal Sodium-Glucose Co-Transport with Empagliflozin Lowers Fasting Plasma Glucose and Improves Beta Cell Function in Subjects With Impaired Fasting Glucose

To examine the effect of renal sodium glucose co-transporter inhibition with empagliflozin on the fasting plasma glucose concentration and beta cell function in subjects with impaired fasting glucose (IFG).8 subjects with normal fasting glucose and 8 subjects with IFG received empagliflozin (25 mg/day) for 2 weeks. Fasting plasma glucose concentration and beta cell function was measured with a 9-step hyperglycemic clamp before and 48 hours and 14 days after the start of empagliflozin.Empagliflozin caused 50±4 and 45±4 grams glucosuria on day 2 in IFG and NFG subjects, respectively, and the glucosuria was maintained for 2 weeks in both groups. The fasting plasma glucose (FPG) concentration decreased only in IFG subjects from 110±2 to 103±3 mg/dl (p<0.01) after 14 days. The FPG concentration remained unchanged (95±2 to 94±2 mg/dl) in NFG subjects. Empagliflozin enhanced beta cell function only in IFG subjects. The incremental area under the plasma C-peptide concentration curve during the hyperglycemic clamp increased by 22±4% and 23±4% after 48 hours and 14 days, respectively (p<0.01); the plasma C-peptide response remained unchanged in NFG subjects. Insulin sensitivity during the hyperglycemic clamp was not affected by empagliflozin in either IFG or NFG. Thus, beta cell function measured with the insulin secretion/insulin sensitivity (disposition) index increased significantly in IFG, but not in NGT subjects.Inhibition of renal sodium-glucose co-transport with empagliflozin in IFG and NFG subjects produces comparable glucosuria but lowers the plasma glucose concentration and improves beta cell function only in IFG subjects.