Effect of dapagliflozin in patients with diabetes and heart failure with mildly reduced or preserved ejection fraction according to background glucose-lowering therapy: A pre-specified analysis of the DELIVER trial

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  • Mats Christian Højbjerg Lassen
  • John W. Ostrominski
  • Silvio E. Inzucchi
  • Brian L. Claggett
  • Ian Kulac
  • Pardeep Jhund
  • Rudolf A. de Boer
  • Adrian F. Hernandez
  • Mikhail N. Kosiborod
  • Carolyn S.P. Lam
  • Felipe A. Martinez
  • Sanjiv J. Shah
  • Akshay S. Desai
  • Magnus Petersson
  • Anna Maria Langkilde
  • Kieran F. Docherty
  • John J.V. McMurray
  • Scott D. Solomon
  • Muthiah Vaduganathan

Aims: Type 2 diabetes (T2D) and heart failure (HF) frequently coexist, but whether clinical outcomes and treatment effects of sodium–glucose cotransporter 2 inhibitors (SGLT2i) vary in relation to background glucose-lowering therapy (GLT) in this population is uncertain. Methods and results: DELIVER randomized patients with HF and left ventricular ejection fraction (LVEF) >40% to dapagliflozin or placebo. The primary outcome was a composite of worsening HF (HF hospitalization or urgent HF visit) or cardiovascular death. In this pre-specified analysis of participants with T2D, treatment effects were assessed by number and class of background GLT(s). Of 3150 participants with T2D at baseline, 22.9% were on no GLT, 36.5% were treated with 1 GLT, and 40.6% with ≥2 GLTs. During follow-up (median: 2.3 years), treatment benefits of dapagliflozin (vs. placebo) on the primary outcome were consistent irrespective of the number of background GLTs (0 GLTs: hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.50–1.00; 1 GLT: HR 1.04, 95% CI 0.80–1.34; ≥2 GLTs: HR 0.71, 95% CI 0.56–0.90; pinteraction = 0.59). Similar findings were observed among participants with (HR 0.73, 95% CI 0.59–0.92) and without background metformin use (HR 0.89, 95% CI 0.72–1.11; pinteraction = 0.22) and in participants with (HR 0.89, 95% CI 0.69–1.16) and without background insulin use (HR 0.78, 95% CI 0.65–0.95; pinteraction = 0.45). Dapagliflozin was well-tolerated irrespective of the number of background GLTs. Conclusions: Dapagliflozin safely and consistently improved clinical outcomes among individuals with T2D and HF with LVEF >40% irrespective of the number and class of background GLTs, and the benefits were not influenced by concomitant metformin or insulin use. These data bolster contemporary guidelines supporting first-line SGLT2i among individuals with T2D and HF, irrespective of background GLT.

Original languageEnglish
JournalEuropean Journal of Heart Failure
ISSN1388-9842
DOIs
Publication statusE-pub ahead of print - 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

    Research areas

  • Dapagliflozin, Diabetes, Heart failure, Medical therapy

ID: 392989238