Cardio-kidney-metabolic protective effects of semaglutide across the spectrum of chronic kidney disease

There is growing evidence suggesting that semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is effective in preventing and treating chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2D). The Evaluate Renal Function with Semaglutide Once Weekly trial demonstrated that semaglutide significantly reduced the risk of major kidney outcomes, including kidney failure, death from kidney or cardiovascular causes, reduced albuminuria and major cardiovascular events. Emerging evidence also suggests a potential kidney-protective effect of GLP-RAs in people without diabetes. Based on this data, contemporary guidelines now support GLP-1RA use, notably semaglutide, as the fourth pillar of diabetic kidney disease (DKD) management in T2D, alongside existing cardio-kidney protective agents (the other 3 pillars of DKD therapy) sodium glucose co-transporter-2 inhibitors, non-steroidal mineralocorticoid receptor antagonists and renin-angiotensin-aldosterone-system blockers. Semaglutide offers complementary and synchronous benefits through distinct mechanisms, underscoring its role in the comprehensive management of patients with T2D. Furthermore, GLP-1RA use in people with T2D and CKD improves metabolic parameters not achievable with the other DKD therapies. This review summarises the clinical evidence for semaglutide's kidney-protective effects in individuals with and without T2D, and highlights recent trial data supporting its broader metabolic effects in CKD. Together these findings position semaglutide as a key agent in modern CKD management.