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

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

doi:10.1002/ejhf.3269

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

Eur J Heart Fail. 2024 May 15. doi: 10.1002/ejhf.3269. Online ahead of print.

Authors

Mats Christian Højbjerg Lassen^{1

2

3}, John W Ostrominski^{1

4}, Silvio E Inzucchi⁵, Brian L Claggett¹, Ian Kulac¹, Pardeep Jhund⁶, Rudolf A de Boer⁷, Adrian F Hernandez⁸, Mikhail N Kosiborod^{9

10}, Carolyn S P Lam¹¹, Felipe A Martinez¹², Sanjiv J Shah¹³, Akshay S Desai¹, Magnus Petersson¹⁴, Anna Maria Langkilde¹⁴, Kieran F Docherty⁶, John J V McMurray⁶, Scott D Solomon¹, Muthiah Vaduganathan¹

Affiliations

¹ Department of Medicine, Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
² Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark.
³ Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁴ Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Section of Endocrinology, Yale University School of Medicine, New Haven, CT, USA.
⁶ BHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
⁷ Erasmus MC, Cardiovascular Institute, Thorax Center, Department of Cardiology, Rotterdam, The Netherlands.
⁸ Duke University Medical Center, Durham, NC, USA.
⁹ Saint Luke's Mid America Heart Institute, Kansas City, MO, USA.
¹⁰ University of Missouri-Kansas City, Kansas City, MO, USA.
¹¹ National Heart Centre Singapore, Duke-National University of Singapore, Singapore, Singapore.
¹² Universidad Nacional de Córdoba, Córdoba, Argentina.
¹³ Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁴ AstraZeneca, Gothenburg, Sweden.

PMID: 38745498
DOI: 10.1002/ejhf.3269

Abstract

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; p_interaction = 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; p_interaction = 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; p_interaction = 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.

Keywords: Dapagliflozin; Diabetes; Heart failure; Medical therapy.

Grants and funding

AstraZeneca Mölndal