Results: The parameter estimates (95% CI) were Gmax: 374 (347, 391) mg/dL; Km: 144 (113, 163) mg/dL; Imax: 0.559 (0.545, 0.607); IC50: 5.28 (3.53, 8.91) nmol/L; FRAC: 0.999 (0.998, 0.999). The calculated RTG for placebo was 230 mg/dL. RTG decreased with increasing empagliflozin concentration; doses of 1, 5, 10, and 25 mg yielded RTG values of 100.5, 43.8, 33.1, and 26.0 mg/dL, respectively. External predictive check demonstrated unbiased prediction of UGE across a range of eGFR values (end-stage renal disease to normal renal function). Simulation indicated that for 10 and 25 mg QD, >50% and 90% of subjects, respectively, maintained steady-state empagliflozin concentrations >IC80 for RTG lowering over the dosing interval.
Conclusions: The model provided a reasonable description of the empagliflozin exposure-UGE response relationship across a broad range of renal function. Empagliflozin significantly lowered the RTG from 230 mg/dL to 33.1 and 26.0 mg/dL for 10 and 25 mg QD respectively, with both doses providing near maximal efficacy.
