Is there a paradigm shift in preventing diabetic heart failure? A review of SGLT2 inhibitors

New Directions in Pharmacological Treatment With SGLT-2 Inhibitor Molecules in the Light of Current Guidelines for Diabetes Mellitus, Heart Failure and Kidney Disease

“…The consequent glycosuria reduces mean plasma glucose levels and decreases glucotoxicity, which improves beta-cell function and insulin sensitivity. Moreover, SGLT-2 inhibition lowers body weight, initially as a result of the diuretic effect and calorie loss, then by increased lipolysis in the adipocytes, which reduces visceral and subcutaneous body fat mass and hence obesity [15,32,77]. In addition to their anti-diabetic effect, the use of SGLT-2 inhibitors has been associated with major cardio-protective mechanisms such as reduction of myocardial stretch and cardiac preload, modest reduction of inflammatory mediators, as well as increased production and myocardial utilization of ketone bodies, which may lead to decreased oxygen demand and improvement in cardiac function [11,17,32].…”

“…Moreover, SGLT-2 inhibition lowers body weight, initially as a result of the diuretic effect and calorie loss, then by increased lipolysis in the adipocytes, which reduces visceral and subcutaneous body fat mass and hence obesity [15,32,77]. In addition to their anti-diabetic effect, the use of SGLT-2 inhibitors has been associated with major cardio-protective mechanisms such as reduction of myocardial stretch and cardiac preload, modest reduction of inflammatory mediators, as well as increased production and myocardial utilization of ketone bodies, which may lead to decreased oxygen demand and improvement in cardiac function [11,17,32]. On the other hand, SGLT-2 inhibitors stabilize renal function by reducing the glomerular hyperfiltration in the early stages of diabetic kidney disease, probably as a result of vasoconstriction in the renal afferent arteriole and decreased post-glomerular vascular resistance [28,45,82].…”