SGLT-2 inhibitors beyond glycemia

Abstract

In the last decade, SGLT-2 inhibitors are a new addition to the armamentarium for the management of Diabetes. Their unique mechanism of action independent of the insulin secretion by the pancreas and acting on the SGLT-2 protein in the proximal convoluted tubule have proved to be an effective anti-glycemic agent. Besides, patients with type II diabetes are at an increased risk of developing heart failure and Diabetes Kidney Disease. This class of drugs has come a long way, proving to be beneficial to cardiovascular and renal outcomes independently of diabetes status. The benefits go far beyond glycemic control, and both the cardio- and nephroprotection are underpinned by diverse mechanisms. From the activation of tubule glomerular feedback and the consequent reduction in hyperfiltration to the improvement of hypoxia and oxidative stress in the renal cortex, SGLT2i has also been shown to inhibit hepcidin and limit podocyte damage. Likewise, they improve cardiac metabolism and bioenergetics, reduce necrosis and cardiac fibrosis, and the production of adipokines, cytokines, and epicardial adipose tissue mass. In terms of outcomes, the efficacy has been demonstrated in blood pressure control, BMI, albuminuria, stroke, heart disease, and mortality rate due to cardiovascular events. Patients with chronic kidney disease and proteinuria, with or without diabetes, treated with some SGLT-2i have a reduced risk of progression. Given these overarching activities on such a broad pathophysiological background and the favorable safety profile that goes with the use of SGLT-2i, it is now certain that they are changing our approach to clinical interventions for important outcomes with an impressive impact.

Keywords: SGLT2 inhibitors, Nephroprotection, Cardiovascular disease