Nephroprotective Properties of the Glucose-Dependent Insulinotropic Polypeptide (GIP) and Glucagon-like Peptide-1 (GLP-1) Receptor Agonists

Abstract

Diabetes mellitus is the leading cause of chronic kidney disease, and about 30–40% of patients with diabetes will develop kidney disease. Incretin hormones have received attention during the past three decades not only as a pharmacotherapy for the treatment of type 2 diabetes, but also for their cardiorenometabolic effects. The main incretins are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Additional to the pancreas, receptors for GLP-1 are widely distributed in various organs, causing positive effects on endothelial function and vascular atherogenesis. Along with glycemic control and weight reduction, GLP-1 receptor agonists also strongly improve cardiovascular and renal outcomes in patients with type 2 diabetes. Recently, a dual GIP and GLP-1 receptor agonist has been approved for the treatment of type 2 diabetes. Compared to GLP-1 receptor agonist semaglutide, dual GIP and GLP-1 receptor agonist tirzepatide showed a superior reduction in hemoglobin A1c and body weight. Preliminary results also suggest that tirzepatide improves kidney outcomes in adults with type 2 diabetes with increased cardiovascular risk. In this review, we present the nephroprotective properties of dual GIP and GLP-1 receptor agonists as a new drug to treat type 2 diabetes.