409-P: Post Hoc Analyses of Longitudinal Changes of Plasma Proteins Associated with Progression to End-Stage Kidney Disease in Type 2 Diabetes Patients with Chronic Kidney Disease Treated with GLP-1 Receptor Agonist Dulaglutide (AWARD-7)

The AWARD-7 clinical trial of patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) reported a slower decline in estimated glomerular filtration rate (eGFR) and decreased urinary albumin-to-creatinine ratio (UACR) in patients treated with dulaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, compared to insulin glargine over one year. Previous studies identified 21 circulating plasma risk proteins highly associated with progression to end stage kidney disease (ESKD) in patients with diabetes (Joslin Kidney Panel). The aim of this study was to determine the longitudinal changes of these proteins in AWARD-7 to evaluate their predictive performance as biomarkers of kidney disease progression. Plasma samples were obtained from patients with T2D and CKD stages 3-4 who received dulaglutide 1.5 mg (n=124) or insulin glargine as basal therapy (n=125) for 52 weeks. Using the Olink custom platform we measured the concentration of 21 proteins at baseline, 26-weeks, and 52-weeks of treatment. At baseline all 21 proteins were correlated with eGFR (r=-0.2 to -0.8; all p<0.0003) and UACR (r=0.2 to 0.6; all p<0.0001). After 26 weeks of treatment, 13 risk proteins significantly increased in glargine group (3 to 13%; all p<0.05) whereas no significant change was observed in dulaglutide group at 26 weeks. By 52 weeks, 5 proteins remained significantly elevated in the glargine group compared to dulaglutide. Several proteins were correlated with declining kidney function (change of eGFR) and increasing UACR in patients with glargine, but not in patients treated with dulaglutide. In this study, the increase of plasma risk proteins associated with ESKD was slowed in dulaglutide-treated patients and is consistent with the hypothesis that several proteins within the Joslin Kidney Panel can serve as predictive biomarkers of treatment efficacy.