Clinical pharmacokinetics and pharmacodynamics of empagliflozin in patients with heart failure

Abstract

AimsThe aim of this work is to compare empagliflozin systemic exposure between patients with heart failure (HF) and patients with type 2 diabetes (T2D).MethodsAnalysis of covariance (ANCOVA) compared steady state trough concentrations of empagliflozin 10 mg in EMPEROR‐reduced (patients with HF with reduced ejection fraction [HFrEF]) and EMPA‐REG OUTCOME (patients with T2D at high cardiovascular risk) after adjusting for eGFR and body weight.ResultsThe difference in geometric Mean (gMean) empagliflozin steady state trough concentration of 10 mg empagliflozin between EMPEROR‐reduced and EMPA‐REG OUTCOME was 1.47‐fold (95% confidence interval [CI]: 1.33, 1.63). Additionally, ANCOVA for the sub‐group of patients with both T2D and HF conditions revealed a difference in gMean steady state trough concentration of 1.53‐fold (95% CI: 1.26, 1.85). In both patients with HFrEF and HF with preserved EF (HFpEF), there was no major difference in empagliflozin steady state trough exposure by New York Heart Association (NYHA) classification or by use of angiotensin receptor‐neprilysin inhibitor as comedication. A weak positive correlation was observed for NT‐proBNP at Week 12 and empagliflozin steady state trough concentration in both patients with HFrEF and HFpEF (Pearson correlation r = 0.19).ConclusionsPlasma concentrations of empagliflozin in patients with HF were higher compared to patients with T2D, but the exposure resulting from the 10 mg dose was still below the exposure resulting from the dose of 25 mg approved in patients with T2D. The difference in exposure was attributable to demographic characteristics and HF‐induced pathophysiological changes. Overall, the results confirm 10 mg as the appropriate empagliflozin dose in patients with HF.