Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Dec 26, 2021; 13(12): 676-694
Published online Dec 26, 2021. doi: 10.4330/wjc.v13.i12.676
Cardiovascular benefits from SGLT2 inhibition in type 2 diabetes mellitus patients is not impaired with phosphate flux related to pharmacotherapy
Mouhamed Nashawi, Mahmoud S Ahmed, Toka Amin, Mujahed Abualfoul, Robert Chilton
Mouhamed Nashawi, Department of Internal Medicine, Baylor Scott and White All Saints Medical Center, Fort Worth, TX 76132, United States
Mahmoud S Ahmed, Toka Amin, Division of Medicine-Cardiology, UT Health San Antonio, San Antonio, TX 78229, United States
Mujahed Abualfoul, Department of Internal Medicine, Faculty of Medicine, Cairo University, Dallas, TX 75203, United States
Robert Chilton, Department of Internal Medicine, Methodist Dallas Medical Center, Dallas, TX 75203, United States
Author contributions: Nashawi M contributed to writing sections pertinent to sodium-glucose cotransporter 2 (SGLT2) inhibition, phosphate metabolism, cardiorenal syndrome, citing findings, writing sections pertinent to pharmacology and Discussion as well as pathophysiology, graphics; Ahmed MS contributed to writing sections pertinent to SGLT2 inhibitor trial data, conducting literature search and interpretation thereof, editing; Amin T contributed to editing, graphics; Abualfoul M contributed to editing and graphics; Chilton R contributed to the framework for publication, editing, clinical perspective on SGLT2 inhibitors, consultation as an interventional cardiologist with respect to the clinical trial data.
Conflict-of-interest statement: The authors do not declare any conflict of interest regarding the publication of this manuscript
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mouhamed Nashawi, MD, Academic Research, Staff Physician, Department of Internal Medicine, Baylor Scott and White All Saints Medical Center, 1400 8th Ave, Fort Worth, TX 76132, United States. nashawi@livemail.uthscsa.edu
Received: April 19, 2021
Peer-review started: April 19, 2021
First decision: July 8, 2021
Revised: August 2, 2021
Accepted: November 30, 2021
Article in press: November 30, 2021
Published online: December 26, 2021
Processing time: 248 Days and 1.5 Hours
Core Tip

Core Tip: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have received increased attention regarding their pleiotropic effects given their markedly impressive performance in cardiovascular outcome trials (CVOT). Preliminary evidence shows that their role as antidiabetic agents is not their sole mechanism in achieving these cardiorenal protective properties. Therefore, investigation in the auxiliary properties that they hold concomitant with glucose control, vindicated by not only CVOTs, but meta-analyses, retrospective studies, and case reports has led to increased interest in delineating their global pharmacodynamic effects across the spectrum of gene expression and molecular modulation to end-organ translational biology. Such a full profile of their effects is not yet understood given the refractory period between clinical evidence supporting their utilization and a proclivity for their implementation in practical clinical environments. In this review, we answer inquiries regarding how via a multifarious avenues, SGLT2 inhibitors, while carrying a negative effect of induced phosphatemia (which is deleterious to the heart), compensate for this phenomenon, retaining their propensity for net cardiac benefit upon pharmacotherapeutic administration under appropriate clinical circumstances.