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Abstract: TH-PO168

AWARD-7 Post Hoc Analysis: Circulating Proteins Measured by Joslin Kidney Panel Identify Dulaglutide Responders

Session Information

Category: Diabetic Kidney Disease

  • 702 Diabetic Kidney Disease: Clinical

Authors

  • McFarlin, Brandon E., Eli Lilly and Company, Indianapolis, Indiana, United States
  • Tye, Sok Cin, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Satake, Eiichiro, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Md Dom, Zaipul, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Ricca, Joseph, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Kechter, Afton V., Eli Lilly and Company, Indianapolis, Indiana, United States
  • Wilson, Jonathan Matthew, Eli Lilly and Company, Indianapolis, Indiana, United States
  • Duffin, Kevin L., Eli Lilly and Company, Indianapolis, Indiana, United States
  • Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States
Background

The AWARD-7 trial demonstrated that the glucagon-like peptide-1 receptor agonist (GLP1-RA) dulaglutide (DULA) can slow the decline in estimated glomerular filtration rate (eGFR) in diabetic patients with chronic kidney disease (CKD). Previously we’ve identified 21 circulating proteins (Joslin Kidney panel – JKP) that are associated with progression to end-stage kidney disease (Kobayashi et al. 2022). We aimed to investigate whether we could leverage the JKP to discern between patients for whom DULA is associated with reduced odds of rapid eGFR decline from those with no impact.

Methods

Plasma samples were obtained from AWARD-7 patients who received DULA 1.5 mg (n=124) or insulin glargine (n=125) for 52 weeks. The 21 JKP was measured using Olink custom-made platform. Proportion of fast decliners (eGFR loss >5.0 ml/min/yr) was evaluated according to plasma concentration of the 21 JKP proteins at baseline, 26- and 52- weeks of the trial.

Results

Concentration of 21 JKP proteins at baseline and 52 weeks did not provide information to predict effectiveness of DULA on reduction of fast decliners. Among patients with above median change in protein concentration from baseline to 26 weeks (26 DELTA), DULA was associated with lower odds of rapid eGFR decline compared with glargine. Specifically, 26 DELTA above median for EHNA4, SYND1, TNF-R1A, -R1B, GFRa1, or DLL1 was associated with significantly lower odds of fast eGFR decline in DULA arm. There was no difference between treatments in patients with below median change in protein concentration.

Conclusion

DULA arm was associated with lower odds of rapid eGFR decline in patients with the greatest change in 6 circulating risk proteins. Further studies are necessary to validate the use of these JKP proteins as effective biomarkers of treatment responders.

Funding

  • Commercial Support – Eli Lilly and Company