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

Research output: Contribution to journalReview articlepeer-review


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

Original languageEnglish (US)
Pages (from-to)676-694
Number of pages19
JournalWorld Journal of Cardiology
Issue number12
StatePublished - Dec 26 2021
Externally publishedYes


  • Canagliflozin
  • Cardiovascular
  • Dapagliflozin
  • Empagliflozin
  • Endothelial
  • Hyperphosphatemia
  • Phosphate
  • Sodium-glucose cotransporter 2

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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