GLP-1 receptor agonists—a potential therapy for chronic kidney disease?

Abstract Chronic kidney disease (CKD) represents a significant health burden worldwide, characterized by a gradual decline in kidney function and increased risk of cardiovascular events. Current therapeutic strategies like inhibition of the renin-angiotensin-aldosterone system or sodium-glucose cotransporter 2 inhibitors (SGLT2i), while beneficial, often fail to fully halt CKD progression, and a significant residual risk of disease progression persists. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for the treatment of type 2 diabetes (T2D), have emerged as promising agents with pleiotropic effects extending beyond glycemic control and weight loss. Evidence from major cardiovascular outcome trials and dedicated CKD studies demonstrates that GLP-1 RAs can confer significant cardiovascular and nephroprotective benefits in patients with T2D and CKD. These benefits include reductions in major adverse cardiovascular events, slowing of kidney disease progression (as measured by estimated glomerular filtration rate (eGFR) decline), and decreased albuminuria. The mechanisms underlying these effects are complex and involve multiple pathways, including anti-inflammatory, anti-fibrotic, and antioxidative actions, as well as improvements in hemodynamic parameters. We provide a comprehensive overview of the current clinical and preclinical evidence supporting the use of GLP-1 RAs in CKD. We discuss the proposed mechanisms of action by which GLP-1 RAs exert their nephroprotective effects and explore the potential for these agents to improve kidney outcomes across a broad spectrum of patients with CKD and critically evaluate the potential risks and safety profile associated with GLP-1 RA use.