Effect of tofogliflozin on cardiac and vascular endothelial function in patients with type 2 diabetes and heart diseases: A pilot study

J Diabetes Investig. 2020 Mar;11(2):400-404. doi: 10.1111/jdi.13122. Epub 2019 Aug 14.


Recent studies have shown that sodium-glucose cotransporter 2 inhibitors decrease the risk of heart failure in patients with type 2 diabetes. However, the precise mechanisms of action of these drugs are not well understood. In the present study, we evaluated the effect of treatment with tofogliflozin for 6 months on cardiac and vascular endothelial function in 26 patients with type 2 diabetes and heart diseases. Tofogliflozin treatment significantly decreased left ventricular end-diastolic dimensions and significantly increased flow-mediated vasodilation. Although E/e' did not significantly change after treatment, the decrease observed in the E/e' ratio was significantly correlated with the increase in acetoacetic acid and 3-hydroxybutyrate levels. These results suggest that sodium-glucose cotransporter 2 inhibitor might improve left ventricular dilatation and vascular endothelial function in patients with type 2 diabetes. Furthermore, it is suggested that the elevation of ketone bodies induced by sodium-glucose cotransporter 2 inhibitors might contribute to a protective effect in left ventricular diastolic dysfunction.

Keywords: Ketone body; Left ventricular diastolic function; Sodium-glucose cotransporter 2 inhibitor.

MeSH terms

  • Aged
  • Benzhydryl Compounds / administration & dosage*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Endothelial Cells / drug effects*
  • Female
  • Glucosides / administration & dosage*
  • Heart Diseases / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Sodium-Glucose Transporter 2 Inhibitors / administration & dosage*
  • Treatment Outcome
  • Ventricular Function, Left


  • Benzhydryl Compounds
  • Glucosides
  • Sodium-Glucose Transporter 2 Inhibitors
  • 6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol