FIG. 1.
The role of sodium glucose cotrasporter-2 (SGLT-2) inhibitors in supply and demand of the heart in type 2 diabetes (T2DM). The top portion of the schematic shows the heart in the dysregulated state of T2DM, with resulting glucolipotoxicity.76 Glucotoxicity occurs when glucose uptake exceeds glucose oxidation.49 Lipotoxicity is characterized by both increased fatty acid delivery and impaired fatty acid oxidation.10 The middle portion represents T2DM treatment with an SGLT-2 inhibitor. Resolution of hyperglycemia leads to decreased myocardial glucose uptake7 and possibly decreased myocardial fatty acid uptake.67 The bottom portion represents the impact of the SGLT-2 inhibitor on the kidneys. SGLT-2 inhibitors enhance lipolysis and fatty acid oxidation in the body.77 Furthermore, a rodent model showing improved left ventricular function after SGLT-2 inhibitor therapy introduces the possibility of these effects in the heart.67 Reabsorption of glucose and sodium is inhibited; their excretion leads to lower serum glucose levels and decreased fluid volume.