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World J Cardiol. Sep 26, 2021; 13(9): 464-471
Published online Sep 26, 2021. doi: 10.4330/wjc.v13.i9.464
Sodium glucose cotransporter 2 inhibitors: New horizon of the heart failure pharmacotherapy
Ryo Naito, Takatoshi Kasai
Ryo Naito, Department of Cardiovascular Biology and Medicine, Cardiovascular Respiratory Sleep Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
Takatoshi Kasai, Department of Cardiovascular Biology and Medicine, Cardiovascular Respiratory Sleep Medicine, Juntendo University Graduate School of Medicine, Sleep and Sleep Disordered Breathing Center, Juntendo University Hospital, Tokyo 113-8421, Japan
Author contributions: Naito R wrote the manuscript; Kasai T revised the manuscript; all authors have read and approved the final manuscript.
Conflict-of-interest statement: Authors have no conflict-of-interest relating to this work.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Takatoshi Kasai, MD, PhD, Associate Professor, Department of Cardiovascular Biology and Medicine, Cardiovascular Respiratory Sleep Medicine, Juntendo University Graduate School of Medicine, Sleep and Sleep Disordered Breathing Center, Juntendo University Hospital, 2-1-1 Hongo Bunkyo-ku, Tokyo 113-8421, Japan. kasai-t@mx6.nisiq.net
Received: March 21, 2021
Peer-review started: March 21, 2021
First decision: May 6, 2021
Revised: May 11, 2021
Accepted: July 23, 2021
Article in press: July 23, 2021
Published online: September 26, 2021
Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have gained momentum as the latest class of antidiabetic agents for improving glycemic control. Large-scale clinical trials have reported that SGLT2 inhibitors reduced cardiovascular outcomes, especially hospitalization for heart failure in patients with type 2 diabetes mellitus who have high risks of cardiovascular disease. Accumulating evidence has indicated that beneficial effects can be observed regardless of the presence or absence of type 2 diabetes mellitus. Accordingly, the Food and Drug Administration approved these agents specifically for treating patients with heart failure and a reduced ejection fraction. It has been concluded that canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin can be recommended for preventing hospitalization associated with heart failure in patients with type 2 diabetes and established cardiovascular disease or those at high cardiovascular risk. In the present review, we explore the available evidence on SGLT2 inhibitors in terms of the cardioprotective effects, potential mechanisms, and ongoing clinical trials that may further clarify the cardiovascular effects of the agents.

Keywords: Sodium glucose cotransporter 2 inhibitors, Heart failure, Clinical trials, Potential mechanisms, Diuretics

Core Tip: Sodium glucose cotransporter 2 inhibitors are newly approved by the Food and Drug Administration as treatment choice for heart failure based on evidence from several large-scale clinical trials demonstrating reduction in cardiovascular outcomes, especially hospitalization for heart failure or cardiovascular death. The background of the approval and potential mechanisms are discussed in this review. As well, summary of available evidence from clinical trials and ongoing trials examining beneficial effects of the agents are written.