Dapagliflozin pharmacokinetics is similar between patients with heart failure with reduced ejection fraction and patients with type 2 diabetes mellitus

Abstract

Dapagliflozin was recently approved for use in adults with chronic heart failure with reduced ejection fraction (HFrEF) with/without type 2 diabetes mellitus (T2DM). The objectives of this analysis were to characterize dapagliflozin pharmacokinetics in patients with HFrEF and to compare dapagliflozin systemic exposure between adults with HFrEF with/without T2DM and adults with T2DM. A nonlinear mixed‐effects modelling approach was applied; the population‐pharmacokinetic model was developed using 9735 dapagliflozin plasma concentrations from 2744 patients. The final two‐compartmental model adequately described the observed dapagliflozin concentrations, with a similar estimated apparent clearance compared with a previous estimate in patients with T2DM without HF and in healthy subjects (23.0 [95% CI: 22.6–23.9] L/h vs. 22.9 [95% CI: 22.1–23.7] L/h). The model‐predicted median area under the dapagliflozin concentration–time profile was ≤1.2‐fold higher in patients with HFrEF vs. those with T2DM without HFrEF, which is not considered clinically relevant. Dapagliflozin exposure was similar between patients with HFrEF with/without T2DM and T2DM patients without HFrEF.