Role of SGLT2 Inhibitors and GLP-1 Analogs in Cardiovascular Risk Reduction in Type 2 Diabetes

Abstract

The leading cause of morbidity and mortality in patients with type-2 diabetes mellitus is cardiovascular (CV) disease, which makes it an important target in management. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonist (GLP-1 RA) are both two new antidiabetic drug classes that showed significant reduction in major cardiovascular events (MACE). With the introduction of these drugs, comprehensive CV risk reduction has been achieved in addition to glucose control. Both drugs work in different ways; the SGLT-2 Inhibitors lead to urinary excretion of 60-90 grams of glucose as well as sodium leading to osmotic diuresis. On the other hand, GLP-1 agonists affect postprandial glucose by enhancing insulin secretion in the beta cells and inhibition of glucagon secretion in the alpha cells in a glucose dependent manner. Different types of drugs are discussed in detail according to different trials such as EMPA-REG, EMPEROR REDUCED, CANVAS, CREDENCE, VERTIS-CV, DAPA-HF and DECLARE TIMI 58 for SGLT-2 Inhibitors, while for GLP-1 agonists, trials such as ELIXA, FREEDOM, EXCEL, LEADER, SUSTAIN, PIONEER 6, REWIND and HARMONY. According to U.S. Drug and Food Administration guidance in 2008, it is required that all new oral hypoglycemic agents undergo cardiovascular outcome trials to evaluate CV safety. Both the SGLT2 inhibitors and GLP-1 agonists have undergone large trials that have led to massive evidence on their cardiovascular safety and renal benefits. The decision on using which drug from both classes depends on different factors like atherosclerotic disease and chronic Kidney disease. Key words. diabetes, cardiovascular, reduction