Semaglutide in Diabetic Kidney Disease: Integrating Clinical Evidence with Mechanistic Insights

Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has demonstrated substantial efficacy in managing type 2 diabetes mellitus (T2DM). It provides glycemic control, promotes weight loss, and offers cardiovascular protection. Evidence also supports its role in diabetic kidney disease (DKD), a leading global cause of end-stage renal disease. DKD arises from a multifactorial interaction involving hyperglycemia, hypertension, and inflammation, which leads to cumulative nephron loss. Beyond glycemic control, semaglutide's mechanisms of action target metabolic and hemodynamic pathways that contribute to renal damage. This review evaluates the preclinical and clinical evidence of semaglutide's role in preventing DKD, focusing on its renal effects and the mechanistic basis for renoprotection. We also position semaglutide within the broader DKD therapeutic landscape by reviewing clinical trial findings, translational studies, real-world evidence, and its effectiveness compared to other drug classes. The expanded actions of semaglutide make it a promising agent in patients with T2DM and DKD and encourage further mechanistic research and long-term evaluation.