Glucagon-Like Peptide-1 Receptor Agonists-Use in Clinical Practice

Abstract

In the past 2 decades, eight glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been approved for the management of type 2 diabetes, each with its peculiar molecular structure, pharmacokinetics, and metabolic effects. Along with their marked glucose-lowering actions, which occur both at fasting and in the postprandial phase without an increased risk of hypoglycemia, GLP-1RAs have provided marked reductions in body weight and ancillary improvements in blood pressure and lipid profile. Recent cardiovascular outcome trials have established the benefits of GLP-1RAs on major cardiovascular events and all-cause mortality, independent of glucose control, with minor effects on preventing hospitalization for heart failure. Novel evidence is also emerging on the protection of GLP-1RAs against diabetic kidney disease, mainly preventing the onset of macroalbuminuria. Several mechanisms have been proposed to explain the cardiorenal protective properties of GLP-1RAs, which may be direct or mediated by additional hemodynamic and anti-inflammatory/antioxidant effects. With their favorable cardiometabolic properties and safety profile, GLP-1RAs may offer an ideal pharmacological option for the management of diabetic kidney disease. In this review, we discuss pharmacokinetic properties, glucometabolic effects, and cardioprotective actions of GLP-1RAs, highlighting the available evidence for a kidney protective role and the proposed mechanisms.

Keywords: Cardiovascular disease; Diabetic kidney disease; Glucagon-like peptide-1 receptor agonists; Glucose-lowering agents; Type 2 diabetes.