Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jun 7;2(3):287-293.
doi: 10.1016/j.jacasi.2022.03.009. eCollection 2022 Jun.

Clinical Benefits of Sodium-Glucose Cotransporter 2 Inhibitors and the Mechanisms Underlying Their Cardiovascular Effects

Yoshiaki Kubota  1 , Wataru Shimizu  1
Affiliations
Review

Clinical Benefits of Sodium-Glucose Cotransporter 2 Inhibitors and the Mechanisms Underlying Their Cardiovascular Effects

Yoshiaki Kubota et al. JACC Asia. .

Abstract

In addition to showing antidiabetic effects, sodium-glucose cotransporter 2 (SGLT2) inhibitors also reduce cardiovascular events in patients with type 2 diabetes mellitus. In major trials of cardiovascular outcomes, SGLT2 inhibitors have been shown to improve cardiovascular and renal outcomes, including reduced rehospitalization in patients with heart failure, regardless of the presence of diabetes. A recent report showed that the benefits of SGLT2 inhibitors in terms of cardiovascular deaths/admissions caused by heart failure and reduced ejection fraction were greater in Asians than in Whites. In this review, the first part demonstrates the results of recent clinical trials and their clinical implications and outlines current trials and upcoming research areas. The second part provides a general overview of the current understanding of the mechanisms of the cardiovascular benefits of SGLT2 inhibitors.

Keywords: ATP, adenosine triphosphate; DPP-4, dipeptidyl peptidase-4; HF, heart failure; HFpEF, HF with preserved ejection fraction; HFrEF, HF with reduced ejection fraction; SGLT2, sodium–glucose cotransporter 2; T2DM, type 2 diabetes mellitus; diabetes; heart failure; sodium–glucose cotransporter 2 inhibitor.

PubMed Disclaimer

Conflict of interest statement

Dr Shimizu has received honorariums and/or scholarship funds from Boehringer Ingelheim Co, Ltd, Daiichi Sankyo Co, Ltd, Ono Pharmaceutical Co, Ltd, Bayer Co, Ltd, Pfizer Co, Ltd, and Bristol-Myers Squibb Co, Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Main Mechanisms of Action of SGLT2 Inhibitors Their metabolic and hemodynamic effects improve myocardial function and reduce the risk of heart failure (details are provided in the text). SGLT2 = sodium–glucose cotransporter 2.
Central Illustration
Central Illustration
Decrease of Cardiac Sympathetic Nerve Activity by SGLT2 Inhibitors There are considered to be 3 mechanisms to decrease the cardiac sympathetic nerve activity by SGLT2 inhibitors, involving a hemodynamic effect, a metabolic (myocardial energy supply) effect, and a hepatic vagus nerve-mediated effect (details are provided in the text). ATP = adenosine triphosphate; SGLT2 = sodium–glucose cotransporter 2.
See this image and copyright information in PMC

References

    1. Braunwald E. The war against heart failure: the Lancet lecture. Lancet. 2015;385:812–824. - PubMed
    1. van Melle J.P., Bot M., de Jonge P., de Boer R.A., van Veldhuisen D.J., Whooley M.A. Diabetes, glycemic control, and new-onset heart failure in patients with stable coronary artery disease: data from the Heart and Soul Study. Diabetes Care. 2010;33:2084–2089. - PMC - PubMed
    1. Seferović P.M., Petrie M.C., Filippatos G.S., et al. Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2018;20:853–872. - PubMed
    1. Dunlay S.M., Givertz M.M., Aguilar D., et al. Type 2 diabetes mellitus and heart failure: a scientific statement from the American Heart Association and the Heart Failure Society of America. Circulation. 2019;140:e294–e324. - PubMed
    1. Echouffo-Tcheugui J.B., Xu H., DeVore A.D., et al. Temporal trends and factors associated with diabetes mellitus among patients hospitalized with heart failure: findings from Get With The Guidelines-Heart Failure registry. Am Heart J. 2016;182:9–20. - PubMed