Sodium-glucose co-transporter-2 inhibitors in heart failure with reduced ejection fraction: Current evidence and future perspectives

Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt

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Background: The sodium-glucose co-transporter-2 (SGLT2) inhibitors were developed as glucose-lowering drugs to treat type 2 diabetes (T2D). However, significant reductions in clinical outcomes have now been demonstrated in patients with heart failure with reduced ejection fraction (HFrEF), irrespective of the presence of T2D. Multiple hypotheses have been proposed for the underlying mechanisms, and the data to support these proposals are emerging. Objectives: To review the clinical outcome data with SGLT2 inhibitors in HFrEF and the data to support the mechanisms for these clinical effects. Methods: Literature review was supported by a PubMed search for relevant articles up to 19 April 2022. Findings: Current data support increased diuresis and reverse cardiac remodelling as important mechanisms for the reductions in heart failure hospitalizations and mortality observed with SGLT2 inhibitors (empagliflozin or dapagliflozin) in patients with HFrEF. Alteration in intrarenal haemodynamic is likely contributing to the observed renoprotective effect of SGLT2 inhibitors. Conclusions: Solid clinical data support the current recommendations to use empagliflozin or dapagliflozin in HFrEF. The underlying mechanisms likely include changes in cardiac and intrarenal haemodynamic. Yet, these mechanisms do not seem to solely explain the observed magnitude of clinical effect with SGLT2 inhibitors in HFrEF, and other mechanisms may contribute.

OriginalsprogEngelsk
TidsskriftBasic and Clinical Pharmacology and Toxicology
Vol/bind131
Udgave nummer1
Sider (fra-til)5-17
Antal sider13
ISSN1742-7835
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
reports grants from The Danish Heart Foundation, Denmark, and The CARDIOHGH at the Department of Cardiology, Herlev and Gentofte University Hospital, Denmark, during the conduct of the submitted work; personal fees from scientific advisory board from AstraZeneca, outside the submitted work; grants from The Research Council at Herlev and Gentofte University Hospital, Denmark; grants from The CARDIOHGH (formerly FUHAS), Herlev and Gentofte University Hospital, Denmark; and grants from The A.P. Møller Foundation for the Advancement of Medical Science, Denmark (as sub‐investigator of the Empire HF trial). reports grants from The Steno Diabetes Center Odense, Denmark (as sub‐investigator of the Empire HF trial). reports personal fees from scientific advisory panel and speaker fees from Boehringer Ingelheim, Merck, Sharp & Dohme, AstraZeneca, Amgen, Novartis, Novo Nordisk and Shire, outside the submitted work. reports personal fees from scientific advisory panel and speaker fees from AstraZeneca, Boehringer Ingelheim, Abbott, Orion Pharma, Pfizer and Novartis, and acting as an unpaid advisor for Corvia, outside the submitted work. reports personal fees from speaker honorarium from Novartis, AstraZeneca, Novo Nordisk and Boehringer Ingelheim, outside the submitted work. reports grants from Abiomed Inc. and personal fees from speaker honorarium from Novartis and Orion Pharma, outside the submitted work. reports grants from The Danish Heart Foundation, Denmark, and from The Capital Region of Denmark, Denmark (as the sponsor and primary investigator of the Empire HF trial); personal fees from speaker honorarium and non‐financial support (as the national lead investigator of the DAPA‐HF trial) from AstraZeneca; and personal fees from speaker honorarium from Novo Nordisk and Boehringer Ingelheim, outside the submitted work. Dr Jensen Dr Omar Dr Kistorp Dr Gustafsson Dr Køber Dr Møller Dr Schou

Funding Information:
Funding was obtained from The Danish Heart Foundation, Denmark [grant number 21‐R150‐A9936‐22197] and The CARDIOHGH at the Department of Cardiology, Herlev and Gentofte University Hospital, Denmark [institutional research grant].

Publisher Copyright:
© 2022 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.

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