Fig. 4

Suggested mechanism for the cardioprotective action of SGLT2 inhibitors. The lowering of blood glucose levels because of suppressed reabsorption in the kidney leads to lower systemic insulin and higher glucagon levels and resurgence of lipolysis resulting in substantial ketogenesis. Increased ketolysis in the heart causes mitochondrial stress followed by a protective (hormetic) response leading to improved mitochondrial function and anti-oxidative capacity which provides significant cardioprotection. SGLT, sodium-glucose co-transporter. (1), (2), (3), see references [129, 155]; (4) and (5), see references [128, 129]; (6), see references [14, 136]; (7), see references [18,19,20,21,22,23,24,25, 156]; (8) and (9), see references [29, 31,32,33,34]; and (10), see references [123,124,125,126,127]