Abstract
Diabetes mellitus is a leading cause of morbidity and mortality and a significant risk factor for the early onset of chronic kidney disease and heart disease. Hyperglycemia and insulin resistance are key factors that play a role in the pathogenesis of type 2 diabetes. Renal glucose reabsorption is a critical component of glycemic regulation. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, commonly known as gliflozins, lower blood sugar levels by inhibiting glucose absorption in the proximal tubule of the kidney. SGLT2 inhibitors are currently used primarily as antidiabetic medications; however, their advantages go well beyond just glycemic control. This article has reviewed the mechanisms behind cardiac and renal involvement in type 2 diabetes and their inseparable interconnections. This article has also discussed the pharmacokinetic and pharmacodynamic profile of different SGLT2 inhibitors available in the market. Finally, this review has provided a perspective on the outcome trials, which provide evidence supporting a potential benefit of SGLT2 inhibitors in reducing cardiovascular and renal risks and possible mechanisms that mediate the renal and cardiovascular protection conferred.
Highlights
BackgroundDiabetes mellitus is a serious and widespread chronic disease caused by an intricate interaction between genes and the environment, as well as other risk factors, including obesity and a sedentary way of life [1]
Sodium-glucose cotransporter 2 (SGLT2) inhibitors constitute a novel class of oral hypoglycemic agents (OHAs) that have been authorized for use in the treatment of T2DM [9]
SGLT2 inhibitors are a novel class of antidiabetic drugs that have shown great potential in treating cardiovascular and renal sequelae in patients with type 2 diabetes
Summary
Diabetes mellitus is a serious and widespread chronic disease caused by an intricate interaction between genes and the environment, as well as other risk factors, including obesity and a sedentary way of life [1]. SGLT2 inhibitors suppress renal glucose reabsorption, enhancing urinary glucose excretion and effectively lowering blood glucose levels [9]. While contributing to hyperglycemia, enhances the absorption and metabolism of free fatty acids by cardiomyocytes, leading to the accumulation of triglycerides and lipotoxicity, which leads to an impairment in cardiac contractility [13] Another important mechanism in diabetes is the formation of AGEs, which act on their receptors, leading to the formation of reactive oxygen species (ROS), promoting inflammation in the myocardium and microcirculation [7]. Chronic kidney disease (CKD), clinically characterized by impaired renal function or elevated urinary excretion of albumin or both, affects approximately half of all patients with T2DM [18].
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