Safety and Efficacy of Semaglutide in Patients With Chronic Kidney Disease, With or Without Type 2 Diabetes: A Systematic Review and Meta‐Analysis

ABSTRACT Background Chronic kidney disease (CKD) affects over half a billion people globally and significantly increases the risk of cardiovascular complications, particularly in those with type 2 diabetes mellitus (T2DM). Although semaglutide, a glucagon‐like peptide‐1 receptor agonist, has shown favourable cardiorenal effects in T2DM patients, prior meta‐analyses were limited by small sample sizes and few studies. This updated meta‐analysis includes both diabetic and non‐diabetic CKD patients, incorporates recently published RCTs and addresses gaps in the literature to enhance result generalizability. Methods MEDLINE, Embase and Cochrane CENTRAL were searched from inception to May 2025 following PRISMA and AMSTAR guidelines. Studies comparing semaglutide with placebo or standard care in adults (≥ 18 years) with CKD, with or without T2DM were included. Primary outcomes included cardiovascular mortality, major adverse cardiovascular events (MACE), major kidney‐related adverse events, nonfatal myocardial infarction and nonfatal stroke. Risk of bias was assessed using Cochrane RoB 2.0. Results Five RCTs involving 12,785 participants were included. The findings showed that semaglutide substantially decreased major kidney‐related adverse events (defined as a composite outcome encompassing the onset of kidney failure (including long‐term dialysis, kidney transplantation or a sustained eGFR reduction to < 15 mL/min/1.73 m 2 ), a sustained 50% or greater reduction in eGFR from baseline, or death due to kidney‐related causes) (RR: 0.79; 95% CI: 0.71–0.87; p < 0.00001; I 2 = 0%), cardiovascular mortality (RR: 0.74; 95% CI: 0.62–0.88; p = 0.0008; I 2 = 36%) and MACE (defined as a composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) (RR: 0.78; 95% CI: 0.70–0.87; p < 0.00001; I 2 = 0%). Conclusion Semaglutide demonstrates a favourable safety profile and significant cardiorenal benefits in CKD patients, with or without T2DM. Further research is needed to confirm its effects in non‐diabetic CKD populations. Trial Registration International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD420251019235