Journal article icon

Journal article

Sodium-glucose co-transporter 2 inhibitor therapy: mechanisms of action in heart failure

Abstract:
Patients with type 2 diabetes mellitus are at a higher risk of developing heart failure compared with the healthy population. In recent landmark clinical trials, sodium-glucose co-transporter 2 (SGLT2) inhibitor therapies improve blood glucose control and also reduce cardiovascular events and heart failure hospitalisations in patients with type 2 diabetes. Intriguingly, such clinical benefits have also been seen in patients with heart failure in the absence of type 2 diabetes although the underlying mechanisms are not clearly understood. Potential pathways include improved glycaemic control, diuresis, weight reduction and reduction in blood pressure, but none fully explain the observed improvements in clinical outcomes. More recently, novel mechanisms have been proposed to explain these benefits that include improved cardiomyocyte calcium handling, enhanced myocardial energetics, induced autophagy and reduced epicardial fat. We provide an up-to-date review of cardiac-specific SGLT2 inhibitor-mediated mechanisms and highlight studies currently underway investigating some of the proposed mechanisms of action in cardiovascular health and disease.
Publication status:
Published
Peer review status:
Peer reviewed

Actions

Access Document

Publisher copy:
10.1136/heartjnl-2020-318060
Publication website:
https://www.research.ed.ac.uk/files/217981001/1032.full.pdf

Authors

More by this author
Role:
Author
ORCID:
0000-0001-9874-6211
More by this author
Role:
Author
ORCID:
0000-0002-4314-9935
More by this author
Institution:
University of Oxford
Role:
Author
ORCID:
0000-0001-7971-4628
More by this author
Role:
Author
ORCID:
0000-0002-7358-9712


More from this funder
Funder identifier:
10.13039/100004440
Grant:
DEN is the recipient of a Wellcome Trust Senior In
More from this funder
Funder identifier:
10.13039/501100000274
Grant:
DEN is supported by the BHF (CH/09/002, RG/16/10/3
More from this funder
Funder identifier:
10.13039/501100000265
Grant:
TS is supported by MRC CRTF (MR/T029153/1)
More from this funder
Funder identifier:
10.13039/100004325
Grant:
SJ is also supported by an investigator initiated
More from this funder
Grant:
The authors are supported by British Heart Foundation [SJ, RE/18/5/3 and FS/CRTF/20/24087; TS, RE/18/5/3; DEN, CH/09/002, RG/18/5/3), Medical Research Council (TS, MR/T029153/1), Wellcome Trust (DEN, WT103782AIA) and an investigator initiated award from AstraZeneca (SJ, SER-19-20118)]


Publisher:
BMJ Publishing Group
Journal:
Heart More from this journal
Volume:
107
Issue:
13
Pages:
1032-1038
Publication date:
2021-02-26
DOI:
EISSN:
1468-201X
ISSN:
1355-6037


Language:
English
Keywords:
Pubs id:
1504633
Local pid:
pubs:1504633
Source identifiers:
W3131396654
Deposit date:
2026-05-12
ARK identifier:
This ORA record was generated from metadata provided by an external service. It has not been edited by the ORA Team.

Terms of use


Views and Downloads






If you are the owner of this record, you can report an update to it here: Report update to this record

TO TOP