Current Insights and Future Directions on the Role of GLP-1 Receptor Agonists in Chronic Kidney Disease

Kavya Rajan,1 Arjun Krishen Jutley,2 Michael W Holliday Jr,3,4 Sankar D Navaneethan3– 5 1Innovation Academy High School, Alpharetta, GA, USA; 2Tomball Memorial High School, Houston, TX, USA; 3Selzman Institute for Kidney Health, Section of Nephrology, Baylor College of Medicine, Houston, TX, USA; 4Renal Section, Medical Care Line, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA; 5Institute of Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USACorrespondence: Sankar D Navaneethan, Baylor College of Medicine, Department of Medicine, Renal Section, 1 Baylor Plaza, Suite 100.37D, Houston, TX, 77030, USA, Email [email protected]: Chronic kidney disease (CKD) incidence continues to rise along with obesity and diabetes, driving substantial medical, psychosocial, and economic burdens for patients. Beyond glycemic control and the recommended therapies of ACEI/ARB, SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a cornerstone therapy to benefit mortality, heart and kidney outcomes. The following review will discuss recent advances to our understanding of the kidney benefits of GLP1 agonism in high-risk populations, including patients with type 2 diabetes mellitus, obesity, those with established cardiovascular disease. Renal signals from cardiovascular outcomes trials disclosed less albuminuria and slower estimated glomerular filtration rate (eGFR) decline with GLP1RA therapy, often additive to sodium–glucose cotransporter-2 inhibition. Dedicated kidney studies now show semaglutide slows CKD progression and lowers mortality in diabetics with CKD, underscoring the relevance of new guidelines that recommend GLP1RA therapy for specific populations. Future priorities should include trials of GLP-1RA in non-diabetic patients with CKD, as well as further evaluation of dual or triple agonists (GLP-1/GIP/glucagon) and clarification of oral GLP1RA efficacy. Overall, GLP-1–based therapies represent a transformative strategy to improve weight, cardiovascular health, and kidney outcomes in diabetic CKD patients.Keywords: cardiorenal outcomes, chronic kidney disease, diabetes, obesity, nephroprotection