Value of SGLT2 Inhibitor (Dapagliflozin) as an Added Therapy in Diabetic Patients With Heart Failure With Reduced Ejection Fraction; Randomized Controlled Clinical Trial

Summary

Type 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for heart failure (HF). Whereas the prevalence of HF in the general population is 1-4%, it reaches approximately 12% in T2DM patients. In 1972, Rubler reported a specific diabetes-associated cardiac injury called diabetic cardiomyopathy. This cardiomyopathy is defined by ventricular dysfunction occurring without coronary disease or hypertension. Diabetic cardiomyopathy is also characterized by left ventricular (LV) hypertrophy, diastolic dysfunction and myocardial fibrosis. A large body of work indicates that diabetic cardiomyopathy is associated with altered cardiac energy metabolism. Indeed, in obese T2DM patients, heart lipid uptake is increased. Several studies support that free fatty acid (FFA) accumulation leads to the increased production of diacylglycerol (DAG), ceramides and reactive oxygen species (ROS), affecting cardiac insulin sensitivity and cardiac contractility. On the other hand, hyperglycemia and glucose overload have been involved in cardiac hypertrophy and dysfunction in the context of T2DM and obesity. The diabetic heart is simultaneously characterized by impaired insulin-stimulated glucose uptake and obvious signs of glucose overload, such as ROS and advanced glycation end-product (AGE) production as well as hexosamine pathway chronic activation. Interestingly, when comparing diabetic and nondiabetic obese patients, we previously demonstrated that hyperglycemia per se plays a central role in the impaired cardiac mitochondrial activity associated with myocardial contractile dysfunction.

Timeline

Start

2020-03

Primary completion

2021-03

Completion

2021-04

Drugs

Indications