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Dulaglutide Effect on Proteins Associated With CKD Progression.

Brandon E McFarlin1, Sok Cin Tye2,3, Eiichiro Satake2,3

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Dulaglutide treatment in type 2 diabetes patients with chronic kidney disease significantly reduced 14 kidney injury proteins, particularly those linked to inflammation. These findings suggest dulaglutide

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Area of Science:

  • Nephrology and Endocrinology
  • Molecular Biology and Proteomics

Background:

  • Type 2 diabetes mellitus (T2D) and chronic kidney disease (CKD) are significant health concerns.
  • The AWARD-7 trial demonstrated dulaglutide's renoprotective effects in T2D patients with moderate-to-severe CKD.
  • Understanding the molecular mechanisms behind dulaglutide's efficacy is crucial for managing kidney disease progression.

Purpose of the Study:

  • To investigate the impact of once-weekly dulaglutide versus insulin glargine on plasma concentrations of 21 key proteins associated with end-stage kidney disease (ESKD) risk.
  • To explore potential biological pathways mediating the renoprotective effects of dulaglutide in T2D patients with CKD.

Main Methods:

  • A post hoc analysis of the AWARD-7 clinical trial data was performed.
  • Plasma samples from participants treated with dulaglutide (n=124) or insulin glargine (n=125) were analyzed using a customized Joslin OLINK proteomic platform.
  • Changes in 21 Joslin Kidney Panel (JKP) protein concentrations from baseline to 6 months were measured and compared between treatment groups.

Main Results:

  • After 6 months, 14 JKP proteins showed significant differences between dulaglutide and insulin glargine groups.
  • Dulaglutide treatment led to a decrease in these 14 JKP proteins, while insulin glargine treatment led to an increase.
  • Notably, 8 tumor necrosis factor (TNF)-receptors and other proteins involved in inflammatory and fibrotic pathways were significantly affected by dulaglutide.

Conclusions:

  • Six months of dulaglutide treatment significantly reduced plasma concentrations of 14 JKP proteins, particularly those in inflammatory and fibrotic pathways.
  • These proteomic changes provide novel insights into the biological mechanisms underlying dulaglutide's renoprotective effects in T2D patients with CKD.
  • The findings support dulaglutide as a therapeutic option for slowing kidney function decline in this patient population.