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Sodium-glucose cotransporter 2 inhibitors’ mechanisms of action in heart failure
Three major cardiovascular outcome trials (CVOTs) with a new class of antidiabetic drugs - sodium-glucose cotransporter 2 (SGLT2) inhibitors (EMPA-REG OUTCOME trial with empagliflozin, CANVAS Program with canagliflozin, DECLARE-TIMI 58 with dapagliflozin) unexpectedly showed that cardiovascular outc...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415232/ https://www.ncbi.nlm.nih.gov/pubmed/32843930 http://dx.doi.org/10.4239/wjd.v11.i7.269 |
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author | Grubić Rotkvić, Petra Cigrovski Berković, Maja Bulj, Nikola Rotkvić, Luka Ćelap, Ivana |
author_facet | Grubić Rotkvić, Petra Cigrovski Berković, Maja Bulj, Nikola Rotkvić, Luka Ćelap, Ivana |
author_sort | Grubić Rotkvić, Petra |
collection | PubMed |
description | Three major cardiovascular outcome trials (CVOTs) with a new class of antidiabetic drugs - sodium-glucose cotransporter 2 (SGLT2) inhibitors (EMPA-REG OUTCOME trial with empagliflozin, CANVAS Program with canagliflozin, DECLARE-TIMI 58 with dapagliflozin) unexpectedly showed that cardiovascular outcomes could be improved possibly due to a reduction in heart failure risk, which seems to be the most sensitive outcome of SGLT2 inhibition. No other CVOT to date has shown any significant benefit on heart failure events. Even more impressive findings came recently from the DAPA-HF trial in patients with confirmed and well-treated heart failure: Dapagliflozin was shown to reduce heart failure risk for patients with heart failure with reduced ejection fraction regardless of diabetes status. Nevertheless, despite their possible wide clinical implications, there is much doubt about the mechanisms of action and a lot of questions to unravel, especially now when their benefits translated to non-diabetic patients, rising doubts about the validity of some current mechanistic assumptions.The time frame of their cardiovascular benefits excludes glucose-lowering and antiatherosclerotic-mediated effects and multiple other mechanisms, direct cardiac as well as systemic, are suggested to explain their early cardiorenal benefits. These are: Anti-inflammatory, antifibrotic, antioxidative, antiapoptotic properties, then renoprotective and hemodynamic effects, attenuation of glucotoxicity, reduction of uric acid levels and epicardial adipose tissue, modification of neurohumoral system and cardiac fuel energetics, sodium-hydrogen exchange inhibition. The most logic explanation seems that SGLT2 inhibitors timely target various mechanisms underpinning heart failure pathogenesis. All the proposed mechanisms of their action could interfere with evolution of heart failure and are discussed separately within the main text. |
format | Online Article Text |
id | pubmed-7415232 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-74152322020-08-24 Sodium-glucose cotransporter 2 inhibitors’ mechanisms of action in heart failure Grubić Rotkvić, Petra Cigrovski Berković, Maja Bulj, Nikola Rotkvić, Luka Ćelap, Ivana World J Diabetes Review Three major cardiovascular outcome trials (CVOTs) with a new class of antidiabetic drugs - sodium-glucose cotransporter 2 (SGLT2) inhibitors (EMPA-REG OUTCOME trial with empagliflozin, CANVAS Program with canagliflozin, DECLARE-TIMI 58 with dapagliflozin) unexpectedly showed that cardiovascular outcomes could be improved possibly due to a reduction in heart failure risk, which seems to be the most sensitive outcome of SGLT2 inhibition. No other CVOT to date has shown any significant benefit on heart failure events. Even more impressive findings came recently from the DAPA-HF trial in patients with confirmed and well-treated heart failure: Dapagliflozin was shown to reduce heart failure risk for patients with heart failure with reduced ejection fraction regardless of diabetes status. Nevertheless, despite their possible wide clinical implications, there is much doubt about the mechanisms of action and a lot of questions to unravel, especially now when their benefits translated to non-diabetic patients, rising doubts about the validity of some current mechanistic assumptions.The time frame of their cardiovascular benefits excludes glucose-lowering and antiatherosclerotic-mediated effects and multiple other mechanisms, direct cardiac as well as systemic, are suggested to explain their early cardiorenal benefits. These are: Anti-inflammatory, antifibrotic, antioxidative, antiapoptotic properties, then renoprotective and hemodynamic effects, attenuation of glucotoxicity, reduction of uric acid levels and epicardial adipose tissue, modification of neurohumoral system and cardiac fuel energetics, sodium-hydrogen exchange inhibition. The most logic explanation seems that SGLT2 inhibitors timely target various mechanisms underpinning heart failure pathogenesis. All the proposed mechanisms of their action could interfere with evolution of heart failure and are discussed separately within the main text. Baishideng Publishing Group Inc 2020-07-15 2020-07-15 /pmc/articles/PMC7415232/ /pubmed/32843930 http://dx.doi.org/10.4239/wjd.v11.i7.269 Text en ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. |
spellingShingle | Review Grubić Rotkvić, Petra Cigrovski Berković, Maja Bulj, Nikola Rotkvić, Luka Ćelap, Ivana Sodium-glucose cotransporter 2 inhibitors’ mechanisms of action in heart failure |
title | Sodium-glucose cotransporter 2 inhibitors’ mechanisms of action in heart failure |
title_full | Sodium-glucose cotransporter 2 inhibitors’ mechanisms of action in heart failure |
title_fullStr | Sodium-glucose cotransporter 2 inhibitors’ mechanisms of action in heart failure |
title_full_unstemmed | Sodium-glucose cotransporter 2 inhibitors’ mechanisms of action in heart failure |
title_short | Sodium-glucose cotransporter 2 inhibitors’ mechanisms of action in heart failure |
title_sort | sodium-glucose cotransporter 2 inhibitors’ mechanisms of action in heart failure |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415232/ https://www.ncbi.nlm.nih.gov/pubmed/32843930 http://dx.doi.org/10.4239/wjd.v11.i7.269 |
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