PMID- 35070111
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220125
IS  - 1949-8462 (Print)
IS  - 1949-8462 (Electronic)
VI  - 13
IP  - 12
DP  - 2021 Dec 26
TI  - Cardiovascular benefits from SGLT2 inhibition in type 2 diabetes mellitus 
      patients is not impaired with phosphate flux related to pharmacotherapy.
PG  - 676-694
LID - 10.4330/wjc.v13.i12.676 [doi]
AB  - The beneficial cardiorenal outcomes of sodium-glucose cotransporter 2 inhibitors 
      (SGLT2i) in patients with type 2 diabetes mellitus (T2DM) have been substantiated 
      by multiple clinical trials, resulting in increased interest in the multifarious 
      pathways by which their mechanisms act. The principal effect of SGLT2i (-flozin 
      drugs) can be appreciated in their ability to block the SGLT2 protein within the 
      kidneys, inhibiting glucose reabsorption, and causing an associated osmotic 
      diuresis. This ameliorates plasma glucose elevations and the negative cardiorenal 
      sequelae associated with the latter. These include aberrant mitochondrial 
      metabolism and oxidative stress burden, endothelial cell dysfunction, pernicious 
      neurohormonal activation, and the development of inimical hemodynamics. Positive 
      outcomes within these domains have been validated with SGLT2i administration. 
      However, by modulating the sodium-glucose cotransporter in the proximal tubule 
      (PT), SGLT2i consequently promotes sodium-phosphate cotransporter activity with 
      phosphate retention. Phosphatemia, even at physiologic levels, poses a risk in 
      cardiovascular disease burden, more so in patients with type 2 diabetes mellitus 
      (T2DM). There also exists an association between phosphatemia and renal 
      impairment, the latter hampering cardiovascular function through an array of 
      physiologic roles, such as fluid regulation, hormonal tone, and neuromodulation. 
      Moreover, increased phosphate flux is associated with an associated increase in 
      fibroblast growth factor 23 levels, also detrimental to homeostatic 
      cardiometabolic function. A contemporary commentary concerning this notion 
      unifying cardiovascular outcome trial data with the translational biology of 
      phosphate is scant within the literature. Given the apparent beneficial outcomes 
      associated with SGLT2i administration notwithstanding negative effects of 
      phosphatemia, we discuss in this review the effects of phosphate on the 
      cardiometabolic status in patients with T2DM and cardiorenal disease, as well as 
      the mechanisms by which SGLT2i counteract or overcome them to achieve their net 
      effects. Content drawn to develop this conversation begins with proceedings in 
      the basic sciences and works towards clinical trial data.
CI  - (c)The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights 
      reserved.
FAU - Nashawi, Mouhamed
AU  - Nashawi M
AD  - Department of Internal Medicine, Baylor Scott and White All Saints Medical 
      Center, Fort Worth, TX 76132, United States. nashawi@livemail.uthscsa.edu.
FAU - Ahmed, Mahmoud S
AU  - Ahmed MS
AD  - Division of Medicine-Cardiology, UT Health San Antonio, San Antonio, TX 78229, 
      United States.
FAU - Amin, Toka
AU  - Amin T
AD  - Division of Medicine-Cardiology, UT Health San Antonio, San Antonio, TX 78229, 
      United States.
FAU - Abualfoul, Mujahed
AU  - Abualfoul M
AD  - Department of Internal Medicine, Faculty of Medicine, Cairo University, Dallas, 
      TX 75203, United States.
FAU - Chilton, Robert
AU  - Chilton R
AD  - Department of Internal Medicine, Methodist Dallas Medical Center, Dallas, TX 
      75203, United States.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - World J Cardiol
JT  - World journal of cardiology
JID - 101537090
PMC - PMC8716977
OTO - NOTNLM
OT  - Canagliflozin
OT  - Cardiovascular
OT  - Dapagliflozin
OT  - Empagliflozin
OT  - Endothelial
OT  - Hyperphosphatemia
OT  - Phosphate
OT  - Sodium-glucose cotransporter 2
COIS- Conflict-of-interest statement: The authors do not declare any conflict of 
      interest regarding the publication of this manuscript
EDAT- 2022/01/25 06:00
MHDA- 2022/01/25 06:01
PMCR- 2021/12/26
CRDT- 2022/01/24 08:51
PHST- 2021/04/19 00:00 [received]
PHST- 2021/08/02 00:00 [revised]
PHST- 2021/11/30 00:00 [accepted]
PHST- 2022/01/24 08:51 [entrez]
PHST- 2022/01/25 06:00 [pubmed]
PHST- 2022/01/25 06:01 [medline]
PHST- 2021/12/26 00:00 [pmc-release]
AID - 10.4330/wjc.v13.i12.676 [doi]
PST - ppublish
SO  - World J Cardiol. 2021 Dec 26;13(12):676-694. doi: 10.4330/wjc.v13.i12.676.