Impact of Empagliflozin on Insulin Use in Patients with Heart Failure with Preserved Ejection Fraction (HFpEF) and Type 2 Diabetes: Sub-Analysis from EMPEROR-Preserved Trial

Abstract

AimWe assessed the impact of empagliflozin on insulin requirement, and outcomes according to insulin use in patients with heart failure with preserved ejection fraction (HFpEF). MethodsOf 5988 patients randomised to empagliflozin or placebo, 2938 (49%) had type 2 diabetes mellitus (T2DM) and 1980 (33%) preDM at baseline. We analysed the effects of empagliflozin vs. placebo on time-to-first sustained insulin initiation in patients with T2DM or preDM not using insulin at baseline. ResultsAt baseline, 861 patients were using insulin. Patients on insulin were younger, had longer DM duration, lower eGFR, and more co-morbidities such as coronary artery disease and macroalbuminuria. During a median observation time of 26 months, among patients with T2DM or preDM not using insulin at baseline, empagliflozin reduced the risk of sustained initiation of insulin by 31% (HR 0.69 [95% CI 0.49, 0.98], p=0.038). Among patients with T2DM, those using insulin at baseline had higher incidence rates of the primary endpoint (first hospitalisation for HF [HHF] or cardiovascular [CV] death), total HHFs and first HHF that were reduced by empagliflozin but still remained higher than in the placebo arm of those not using insulin. Beneficial effects of empagliflozin on CV outcomes did not differ by baseline insulin use. ConclusionsEmpagliflozin reduced the rate of insulin initiation by 31% in patients with HFpEF and T2DM or preDM. Insulin-users at baseline were at higher risk of adverse CV outcomes; still, the effects of empagliflozin on CV outcomes were consistent in patients with T2DM irrespective of insulin treatment.Figure: The effect of empagliflozin vs placebo on clinical outcomes and mortality in patients with HFpEF and baseline T2DM with or without insulin.