Data from five randomized, placebo-controlled, multiple oral dose studies of 
empagliflozin in patients with type 2 diabetes mellitus (T2DM; N = 974; 1-100 mg 
q.d.; ≤12 weeks) were used to develop a population pharmacokinetic (PK) model 
for empagliflozin. The model consisted of two-compartmental disposition, lagged 
first-order absorption and first-order elimination, and incorporated appropriate 
covariates. Population estimates (interindividual variance, CV%) of oral 
apparent clearance, central and peripheral volumes of distribution, and 
inter-compartmental clearance were 9.87 L/h (26.9%), 3.02 L, 60.4 L (30.8%), and 
5.16 L/h, respectively. An imposed allometric weight effect was the most 
influential PK covariate effect, with a maximum effect on exposure of ±30%, 
using 2.5th and 97.5th percentiles of observed weights, relative to the median 
observed weight. Sex and race did not lend additional description to PK 
variability beyond allometric weight effects, other than ∼25% greater oral 
absorption rate constant for Asian patients. Age, total protein, and 
smoking/alcohol history did not affect PK parameters. Predictive check plots 
were consistent with observed data, implying an adequate description of 
empagliflozin PKs following multiple dosing in patients with T2DM. The lack of 
marked covariate effects, including weight, suggests that no exposure-based dose 
adjustments were required within the study population and dose range.