Dulaglutide Effect on Proteins Associated With CKD Progression
Kidney International Reports, 2026
McFarlin B., Tye S., Satake E., Md Dom Z., Kechter A., Wilson J., Krolewski A., Duffin K.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Metabolic Diseases Nephrology | Pathophysiology | Plasma | O Olink Flex |
Abstract
Background
In the AWARD-7 clinical trial in participants with type 2 diabetes (T2D) and moderate-to-severe chronic kidney disease (CKD), a once-weekly treatment with dulaglutide (Dula) slowed kidney function decline compared to insulin glargine (glargine). This post-hoc study evaluated Dula’s effect on 6-month changes in plasma concentrations of 21 Joslin Kidney Panel (JKP) proteins, which were previously associated with end-stage kidney disease risk.
Methods
Plasma concentrations of JKP proteins in participants treated with Dula (n=124) and glargine (n=125) were measured using a custom OLINK proteomics platform. Changes in circulating JKP protein concentrations from baseline to 6 months were determined.
Results
Baseline JKP protein concentrations were similar between groups. After 6 months, 14 JKP proteins increased in the glargine group and decreased in the Dula group with statistically significant between-group differences. The most significant differences were observed for eight TNF-receptors (TNF-R1, -R2, -R3, -R4, -R6B, -R7, -R19L, -R27), key mediators of inflammatory and apoptotic pathways. Additionally, CD160, WFDC2, DLL1, LAYN, SYND1, and EPHA2 were significantly different between treatments, although to a lesser degree, and seven other proteins remained unaffected. Kidney Injury Molecule 1 (KIM1), a marker of proximal tubule stress, declined in both groups without significant differences. Treatment effects were more pronounced in participants with lower baseline eGFR or higher baseline UACR, HbA1c, or BMI.
Conclusions
Six months of Dula treatment significantly lowered concentrations of 14 JKP proteins, particularly those involved in inflammatory and fibrotic pathways. These findings provide insight into biological mechanisms that may underlie the reno-protective effects of dulaglutide.