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

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), 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 = 0%), cardiovascular mortality (RR: 0.74; 95% CI: 0.62-0.88; p = 0.0008; I = 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 = 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.