Efficacy and Safety of
GLP
‐1 Receptor Agonists on Combined Cardiovascular and Renal Outcomes in Patients With Chronic Kidney Disease: A Systematic Review and Meta‐Analysis
Rashpinder Kaur, Avtar Singh ABSTRACT
Aims
Chronic kidney disease (CKD) confers substantial cardiovascular and renal morbidity. GLP‐1 receptor agonists (GLP‐1 RAs) have demonstrated cardiorenal protection across major randomised trials, culminating in the landmark FLOW trial. No prior systematic review has simultaneously synthesised cardiorenal outcomes in a CKD‐restricted population, executed a network meta‐analysis for agent‐level comparisons, or assessed whether SGLT2 inhibitor background therapy modifies treatment effects.
Materials and Methods
MEDLINE, Embase, Cochrane CENTRAL, and Web of Science were searched through March 2025. Eligible RCTs enrolled adults with CKD (eGFR < 60 mL/min/1.73 m 2 or UACR ≥ 30 mg/g) comparing GLP‐1 RAs versus placebo for ≥ 26 weeks. Primary outcomes were 3‐point MACE and a KDIGO‐harmonised composite kidney endpoint. Random‐effects pairwise meta‐analyses and a frequentist NMA were performed. GRADE certainty was assigned to all outcomes.
Results
Thirteen RCTs (97 428 participants; 31 846 with confirmed CKD) were included. GLP‐1 RAs reduced MACE by 16% (HR 0.84, 95% CI 0.79–0.89; high certainty) and the composite kidney endpoint by 21% (HR 0.79, 95% CI 0.73–0.86; high certainty). Kidney failure risk was reduced by 28% (HR 0.72); UACR decreased by 26%. Benefits were consistent irrespective of SGLT2 inhibitor background use (interaction p = 0.41). Semaglutide ranked highest in the NMA (SUCRA 78.4%). No excess acute kidney injury risk was observed.
Conclusions
GLP‐1 RAs provide clinically meaningful cardiorenal protection in CKD, additive to SGLT2 inhibitor benefits. In exploratory network meta‐analysis, semaglutide subcutaneous achieved the highest SUCRA ranking for kidney composite outcomes; the direct semaglutide evidence is rated high certainty by GRADE.