GLP-1 Receptor Agonists in Diabetic Nephropathy: Clinical Evidence, Molecular Mechanisms, and Future Perspectives

Diabetic nephropathy (DN) remains the predominant etiology of chronic kidney disease (CKD) worldwide, significantly resulting in mortality and morbidity among individuals with diabetes mellitus. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have surfaced as transformative treatment options, offering multifaceted benefits that extend beyond glycemic control. This article explores the comprehensive role of GLP-1RAs in renoprotection and their impact on the progression of DN. Glucagon-like peptide-1 receptor agonists exhibit significant renoprotective effects through multiple mechanisms, including glycemic optimization (HbA1c reduction of 0.73%-3.01%), substantial weight reduction (14%-16% in leading clinical trials), blood pressure reduction (2-6 mmHg systolic reduction), anti-inflammatory effects, and direct albuminuria reduction (11.74%-33%). Major clinical trials, including Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN-6), Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER), Evaluate Renal Function with Semaglutide Once Weekly (FLOW), Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND), consistently demonstrate cardiovascular benefits and slowed CKD progression. Glucagon-like peptide- 1 receptor agonists signify a vital shift in the management of diabetic kidney disease, offering comprehensive metabolic benefits with established renoprotective and cardiovascular advantages.

Cite this article as: Mathew GG. GLP-1 receptor agonists in diabetic nephropathy: clinical evidence, molecular mechanisms, and future perspectives. Turk J Nephrol. 2026;35(3):182-193.