Empagliflozin and Kinetics of Renal Glucose Transport in Healthy Individuals and Individuals With Type 2 Diabetes

Abstract

Renal glucose reabsorption was measured with the stepped hyperglycemic clamp in 15 subjects with type 2 diabetes mellitus (T2DM) and 15 without diabetes after 2 days and after more chronic (14 days) treatment with empagliflozin. Patients with T2DM had significantly greater maximal renal glucose transport (TmG) compared with subjects without diabetes at baseline (459 ± 53 vs. 337 ± 25 mg/min; P < 0.05). Empagliflozin treatment for 48 h reduced the TmG in both individuals with and without diabetes by 44 ± 7 and 53 ± 6%, respectively (both P < 0.001). TmG was further reduced by empagliflozin in both groups on day 14 (by 65 ± 5 and 75 ± 3%, respectively). Empagliflozin reduced the plasma glucose concentration threshold for glucose spillage in the urine similarly in individuals with T2DM and without diabetes to <40 mg/dL, which is well below the normal fasting plasma glucose concentration. In summary, sodium-glucose transporter-2 inhibition with empagliflozin reduces both TmG and threshold for glucose spillage in the urine in patients with T2DM and those without diabetes.

Trial registration: ClinicalTrials.gov NCT01867307.

© 2017 by the American Diabetes Association.

Figures

Figure 1

GFR (creatinine clearance) and urinary excretion of sodium and chloride in subjects without diabetes and with T2DM at baseline, on the day that empagliflozin (EMPA) was started (day 0), and during the 24–48-h period (day 1) after the start of empagliflozin. *P < 0.01 vs. baseline; †P < 0.05 vs. baseline.

Figure 2

UGE (top) and fractional excretion of glucose (bottom) during the hyperglycemic clamp in subjects without diabetes (left) and with T2DM (right) at baseline and at 48 h and 14 days after the start of empagliflozin. The plasma glucose concentration during each of the nine steps of the hyperglycemic clamp is shown on the horizontal axis.

Figure 3

Renal glucose reabsorption is plotted as a function of the plasma glucose concentration during the hyperglycemic clamp in subjects without diabetes (left) and with T2DM (right) at baseline and at 48 h and 14 days after the start of empagliflozin.

Figure 4

Maximum Tm (top) and renal threshold (bottom) for glucose spillage into the urine in subjects without diabetes and with T2DM at baseline and at 48 h and 14 days after the start of empagliflozin. #P < 0.05 vs. subjects without diabetes; *P < 0.0001 vs. baseline; $P < 0.05 vs. 48 h.