GLP‑1 Receptor Agonists in Non‑Diabetic Chronic Kidney Disease: A Systematic Review

Introduction: Glucagon- like peptide- 1 receptor agonists have demonstrated cardiovascular and kidney benefits in type 2 diabetes, but their role in non- diabetic chronic kidney disease remains uncertain. Methodology: A systematic review following PRISMA 2020 guidelines was conducted, in which MEDLINE (PubMed), Cochrane Library, TRIP and NICE databases were used. Search strategies combined MeSH terms and free- text strategies. Eligible studies included randomized controlled trials, observational studies, systematic reviews, meta- analyses and clinical practice guidelines published in English, Portuguese or Spanish. A thorough examination of reference lists was conducted to identify additional studies. Evidence was graded using the Strength of Recommendation Taxonomy. Results: The final synthesis included two placebo-controlled randomized trials. In the SELECT trial, non- diabetic adults with overweight or obesity and established cardiovascular disease who received semaglutide 2.4mg2.4mg once weekly showed a slower decline in estimated glomerular filtration rate and approximately 22%22% fewer composite kidney events compared with placebo, with a greater benefit in those with baseline estimated glomerular filtration rate below 60mL/60mL/ min/1.73m2min/1.73m2 . In the SMART trial, adults with non- diabetic chronic kidney disease and overweight or obesity experienced a 52%52% reduction in albuminuria at 24 weeks with semaglutide, while measured and estimated glomerular filtration rate remained stable. Conclusion: These findings suggest potential benefits of glucagon-like peptide- 1 receptor agonists on albuminuria and kidney function trajectories independent of diabetes, but effects on long- term kidney outcomes remain unknown. Use in this population should be individualized and further studies are required to validate this use.