SGLT2 inhibitors for the prevention and treatment of heart failure: A scientific statement of the HFA and the HFAI

Metra M. Tomasoni D. Adamo M. Amir O. Anker S.D. Bayes-Genis A. Boehm M. Butler J. Chioncel O. Filippatos G. Gustafsson F. Jankowska E.A. Kaski J.C. Moura B. Petrie M.C. Ponikowski P. Rakisheva A. Ristic A. Roubille F. Savarese G. Seferovic P. van der Meer P. Volterrani M. Coats A.J. Chopra V.K. Rosano G.
December 2025 John Wiley and Sons Inc

ESC Heart Failure
2025 #12 Issue 6 3806 - 3825 pp.

In the 2021 European Society of Cardiology (ESC) heart failure (HF) guidelines, sodium–glucose cotransporter 2 (SGLT2) inhibitors were recommended for the prevention of HF in patients with type 2 diabetes mellitus (T2DM) and for the treatment of HF with reduced ejection fraction (HFrEF). Further trials showed efficacy of empagliflozin and dapagliflozin in patients with HF with preserved ejection fraction (HFpEF). These results prompted a broadened recommendation for the SGLT2 inhibitors dapagliflozin or empagliflozin across the whole left ventricular ejection fraction (LVEF) spectrum in the 2023 Focused Update of the ESC HF guidelines and in other international guidelines. In SOLOIST-WHF and EMPULSE, sotagliflozin (enrolling only patients with T2DM) and empagliflozin, respectively, were beneficial when initiated at the end or soon after an episode of decompensated HF. Based on these results and on the early appearance of their beneficial effects, the administration of SGLT2 inhibitors should start early in patients hospitalized for acute HF. Analyses after study drug withdrawal in randomized clinical trials have shown that their benefits may decline rapidly after discontinuation, and thus, persistence of treatment is advised. In EMPACT-MI, empagliflozin did not reduce the primary outcome of cardiovascular (CV) death/HF hospitalization but reduced first/recurrent HF hospitalizations. Potential benefits of SGLT2 inhibitors in further specific conditions (i.e., cardiac amyloidosis, grown-up congenital heart disease and paediatric patients with HF) have been reported in observational studies but need confirmation from prospective trials. This scientific statement summarizes current evidence regarding the effects of SGLT2 inhibitors for the prevention and treatment of HF.

GDMT , heart failure , prevention , SGLT2 inhibitors , treatment

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Cardiology. ASST Spedali Civili di Brescia and Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy
Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
Department of Cardiology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
Department of Cardiology (CVK) of German Heart Center Charité, German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité—Universitätsmedizin Berlin, Berlin, Germany
Heart Institute, Hospital Universitari Germans Trias i Pujol, Badalona, CIBERCV, Barcelona, Spain
Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg, Germany
Baylor Scott & White Research Institute, Dallas, TX, United States
University of Mississippi, Jackson, MS, United States
Emergency Institute for Cardiovascular Diseases ‘Prof. C.C. Iliescu’, University of Medicine Carol Davila, Bucharest, Romania
School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
Department of Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Institute of Heart Diseases, Wrocław Medical University, Wrocław, Poland
Molecular and Clinical Sciences Research Institute, St Georges University of London, London, United Kingdom
Centro de Investigação em Tecnologias e Serviços de Saúde, Porto, Portugal
Serviço de Cardiologia, Hospital das Forças Armadas—Pólo do Porto, Porto, Portugal
School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom
Department of Cardiology, Wrocław Medical University, Wrocław, Poland
Department of Cardiology, Scientific Institution of Cardiology and Internal Diseases, Almaty, Kazakhstan
School of Medicine, University of Belgrade, Belgrade, Serbia
PhyMedExp, Université de Montpellier, INSERM, CNRS, Cardiology Department, CHU de Montpellier, Montpellier, France
Serbian Academy of Sciences and Arts, Belgrade, Serbia
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Department of Medical Sciences, Centre for Clinical and Basic Research, IRCCS San Raffaele Pisana, Rome, Italy
Heart Research Institute, Newtown, NSW, Australia
Department of Cardiology, Medanta, Haryana, Gurgaon, India
Department of Human Sciences and Promotion of Quality of Life, San Raffaele Open University of Rome, Rome, Italy
IRCCS San Raffaele, Rome, Italy

Cardiology. ASST Spedali Civili di Brescia and Department of Medical and Surgical Specialties
Department of Clinical Science and Education
Department of Cardiology
Department of Cardiology (CVK) of German Heart Center Charité
Heart Institute
Klinik für Innere Medizin III
Baylor Scott & White Research Institute
University of Mississippi
Emergency Institute for Cardiovascular Diseases ‘Prof. C.C. Iliescu’
School of Medicine
Department of Cardiology
Institute of Heart Diseases
Molecular and Clinical Sciences Research Institute
Centro de Investigação em Tecnologias e Serviços de Saúde
Serviço de Cardiologia
School of Cardiovascular and Metabolic Health
Department of Cardiology
Department of Cardiology
School of Medicine
PhyMedExp
Serbian Academy of Sciences and Arts
Department of Cardiology
Department of Medical Sciences
Heart Research Institute
Department of Cardiology
Department of Human Sciences and Promotion of Quality of Life
IRCCS San Raffaele

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