Diabetes mellitus type 2, is a metabolic disorder with an estimated number of 400 million patients worldwide associated with insulin resistance, hyperglycemia, and decreased insulin secretion from β pancreatic cells. T2DM is prevalently correlated with micro and macrovascular complications, especially heart failure (HF). The correlation between diabetes mellitus and heart failure is a result of chronic glucotoxicity, lipotoxicity, and altered insulin signaling including myocardial derangement caused by oxidative stress, inflammation, advanced glycation end products, etc.  T2DM patients retain more glucose in the kidney due to glycemic deprivation in their bodies. 

SGLT2 inhibitors (Sodium-Glucose Co-Transporters Inhibitors) are oral antidiabetic drugs that decrease glucose reabsorption and promote osmotic diuresis and natriuresis, therefore, increasing the excretion of glucose from the body. SGLT2 are insulin-independent drugs and solely dependent on renal glomerular tubular functions. Several studies have stipulated that SGLT2 increases myocardial metabolism, mitochondrial calcium levels, cardiac efficiency, and renal functions.

In 2010, Dapagliflozin (DAPA), an SGLT2 inhibitor entered phase III trials. In the study conducted by Ferrannini et al., three different dosages:2.5, 5, 10 mg, and placebo were tested in two study groups. The first group was further divided into main and exploratory groups who received the placebo or one of the three doses daily in the morning and evening respectively. The second group received 5 mg or 10 mg of DAPA daily in the morning. Though the study was not able to highlight a significant dosing time, it highlighted the DAPA’s potential to lower hyperglycemia in diabetic patients.

After its FDA approval in 2014, DAPA was clinically tested in a multicentred trial in 33 countries in 2018 to evaluate its effect on heart failure.17,000+ patients were enrolled in the trial with a unique group of 10,000+ patients without any history of CV disease. The trial revealed DAPA to be superior to placebo when both were given in the amount of 10 mg in an equally i.e., 1:1 DAPA- placebo group. The study reported less frequent (4.9%) hospitalization and HF deaths compared to placebo (5.8%). This study favored the ability of DAPA in preventing hospitalization for heart failure.

Source: Keller D. M et al., J. Clin. Med.2022, 11(6)