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Early cardiovascular outcome trials of GLP-1RAs for diabetes included secondary kidney endpoints, typically defined by a 5-point composite renal outcome (CRO): increased urinary albumin-to-creatinine ratio, new-onset macroalbuminuria, sustained decline in estimated glomerular filtration rate (eGFR), initiation of chronic renal replacement therapy, and renal death.[15, 16] In patients with T2DM, GLP-1RAs significantly reduced CRO incidence, primarily driven by an 18% reduction in new-onset macroalbuminuria.[47] More recently, the FLOW trial, a dedicated kidney outcome trial in patients with T2DM and CKD, was terminated early due to overwhelming efficacy and mortality benefit.[24] FLOW revealed that semaglutide reduced the risk of a composite kidney outcome by 24% compared to placebo.[24] Emerging data suggest GLP-1RAs may also offer kidney benefits in populations without diabetes.[48] The SELECT trial demonstrated a reduced risk of persistent eGFR decline in patients with obesity and cardiovascular disease treated with semaglutide.[15] Additionally, a meta-analysis of placebo-controlled RCTs reported a slower decline in eGFR over one year in individuals with a baseline eGFR 3060 mL/min/1.73m 2 treated with GLP-1RAs regardless of diabetes status.[12] These findings support the potential utility of GLP-1RAs in CKD patients without diabetes, and additional dedicated trials are underway to validate these outcomes in populations without diabetes

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