Fig. 3.

Postulated mechanisms for the nondiabetic action of SGLT2 inhibitors. SGLT2 inhibitors have both cardioprotective and renoprotective effect in addition to metabolic effect. The cardioprotective effect includes direct cardiovascular effect as well as indirectly through action on renal system and is manifested through improvement of cardiac parameters, decrease in heart failure as well as promotion of cardiac remodeling. Renal effect is through both direct and indirect pathways resulting in glycosuria, nitrituria, decrease in proteinuria, inflammation, vasodilation, decrease preload, hormonal effect as well as increased hematocrit and erythropoietin. Some of the metabolic effects included decreased BMI, decreased adiposity, change in appetite and weight among others. (Abbreviations: NF-κB – Nuclear factor kappa B; MCP-1 – Monocyte chemoattractant protein-1; TGF-β – Transforming growth factor β; NEFA – Non-esterified fatty acids; NO – Nitric oxide; Na – Sodium; O₂ – Oxygen; N₂ – Nitrogen; LDL – Low density lipoprotein; HDL – High density Lipoprotein;↑– increase in; ↓ – decrease in).