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

GLP-1 receptor agonists lowered the risk of major cardiovascular events and of a combined kidney-failure/progression outcome in people with chronic kidney disease; benefits were similar whether or not patients were also taking SGLT2 inhibitors. The conclusions come from 13 randomised trials, and semaglutide ranked highest in an exploratory comparison of specific agents.

Systematic review — systematic review and network meta-analysis. Population: adults with chronic kidney disease (eGFR <60 mL/min/1.73 m2 or UACR ≥30 mg/g) from randomised controlled trials. Sample size: 97,428 participants; 31,846 with confirmed CKD. Interventions: GLP-1 receptor agonists.

Across 13 RCTs (97,428 participants; 31,846 with CKD), GLP-1 RAs reduced MACE by 16% (HR 0.84, 95% CI 0.79-0.89) and the composite kidney endpoint by 21% (HR 0.79, 95% CI 0.73-0.86), both with high certainty. Kidney failure risk was reduced by 28% (HR 0.72) and UACR decreased by 26%. Benefits were consistent irrespective of SGLT2 inhibitor background use (interaction p = 0.41). Semaglutide ranked highest in the network meta-analysis (SUCRA 78.4%). No excess acute kidney injury risk was observed.

Semaglutide researchers will use this meta-analysis as high-certainty evidence that GLP-1 receptor agonism, including semaglutide, reduces cardiorenal events in chronic kidney disease and appears additive to SGLT2 inhibition. It does not establish semaglutide as definitively superior to other GLP-1 RAs, and the network ranking is exploratory. It provides no dosing or treatment-sequencing advice.

Key findings

• GLP-1 receptor agonists reduced 3-point MACE by 16% (HR 0.84, 95% CI 0.79-0.89; high certainty).
• They reduced 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%.
• Effects were consistent irrespective of SGLT2 inhibitor background therapy (interaction p = 0.41).
• Semaglutide ranked highest in the network meta-analysis (SUCRA 78.4%).

Limitations

• Agent-level network meta-analysis rankings rely largely on indirect comparisons rather than head-to-head trials.
• Semaglutide's highest SUCRA ranking is exploratory and not definitive evidence of superiority.
• Included trials required at least 26 weeks of follow-up, so longer-term effects are not captured here.
• The abstract does not report assessment of publication bias or heterogeneity across trials.

The record

• Journal: Diabetes, obesity & metabolism 28(9): 8337-8346
• Published: 2026-06-23
• PMID: 42337824 — DOI: 10.1111/dom.71031
• MeSH terms: Kidney, Humans, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Hypoglycemic Agents, Treatment Outcome, Renal Insufficiency, Chronic, Randomized Controlled Trials as Topic, Sodium-Glucose Transporter 2 Inhibitors, Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide
• Author countries: UK

Peptide profiles: Semaglutide.

All indexed evidence: Semaglutide trials & papers.

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