Real-World Evidence for Improvements in Inflammation and Anemia Biomarkers After the Initiation of GLP-1RA in Patients on Hemodialysis

Rationale & Objective Glucagon-like peptide-1 receptor agonists are increasingly used for diabetes and obesity but have not been studied in patients with kidney failure with replacement therapy on hemodialysis in prospective trials. Glucagon-like peptide-1 receptor agonists may influence inflammatory pathways relevant to anemia, although their effects in hemodialysis patients remain unclear. Study Design Retrospective matched cohort study. Setting & Participants Data were derived from a large U.S. dialysis provider (Fresenius Kidney Care). We identified 2,468 adult patients who initiated glucagon-like peptide-1 receptor agonists therapy between January 1, 2023, and November 1, 2024, and matched 1:1 to non-users using propensity scores based on demographics, comorbidities, and baseline laboratory values. Exposure Initiation of glucagon-like peptide-1 receptor agonist therapy. Outcomes Longitudinal changes over 12 months in inflammatory markers (neutrophil-to-lymphocyte ratio [NLR], white blood cell [WBC] count, albumin) and anemia parameters (hemoglobin, ferritin, transferrin saturation [TSAT], ESA dose, and erythropoietin resistance index [ERI]). Analytical Approach Linear mixed models were used to compare longitudinal trajectories between matched groups. Results Compared to matched controls, glucagon-like peptide-1 receptor agonist users demonstrated reductions in systemic inflammation, characterized by lower NLR (3.97 vs. 4.64), with a mean difference of -0.67 (95% CI: -0.89 to -0.45)) and WBC counts at 12 months, alongside greater improvements in serum albumin (3.92 vs. 3.86 g/dL, with a mean difference of 0.06 (95% CI: 0.04 to 0.08)). While hemoglobin levels remained comparable between groups (10.9 vs. 10.84 g/dL, with a mean difference of 0.06 (95% CI: -0.004 to 0.12)), glucagon-like peptide-1 receptor agonist users had lower cumulative ESA exposure (1,881.9 vs. 2,005.8 mcg; mean difference −123.9 mcg, 95% CI: −201.7 to −46.1)mcg) and a modest reduced rate of ERI compared to non-users. Additionally, iron stores (ferritin and TSAT) were consistently higher in the glucagon-like peptide-1 receptor agonist group. Conclusions In patients receiving maintenance hemodialysis, glucagon-like peptide-1 receptor agonists use was associated with reductions in inflammatory markers and lower ESA requirements; however, as an observational study, causality cannot be inferred. These findings suggest glucagon-like peptide-1 receptor agonists may have potential benefits of managing inflammation and inflammation-mediated anemia in kidney failure.