Introduction and Objective: In the SURPASS-4 clinical trial in patients with type 2 diabetes (T2D) at high cardiovascular risk, once-weekly treatment with the dual GLP-1/GIP receptor agonist, tirzepatide (TZP) resulted in substantial weight reduction, slower kidney function decline, and reduced albuminuria compared to insulin glargine. This post-hoc analysis evaluated the effect of TZP on 52-week changes in plasma concentrations of 21 circulating proteins from the Joslin Kidney Panel (JKP), which were strongly associated with the risk of end-stage kidney disease in diabetes.Methods: Plasma concentrations of JKP proteins were measured at baseline and 52 weeks in patients treated with TZP (n=104) or insulin glargine (n=106) using the custom Joslin OLINK proteomics platform version 2. Changes in JKP protein concentrations from baseline to 52 weeks were calculated and compared between treatment groups.Results: At baseline, plasma concentrations of JKP proteins were similar in both treatment groups. Over 52 weeks of treatment, concentrations of 7 out of 21 proteins decreased in TZP group compared to glargine group. The differences in 52-week changes between treatment groups were larger and more statistically significant for the 12 JKP proteins in patients with high baseline UACR (Table).Conclusion: Fifty-two weeks of treatment with TZP significantly lowered concentrations of 12 out of 21 circulating JKP v2 proteins in T2D patients.
E. Satake: None. S. Tye: None. I. Pavo: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. A. Nowak-Szwed: None. L. Bowsman: Employee; Current; Eli Lilly and Company. J. Wilson: Employee; Current; Lilly. F. Fleming: Employee; Current; Renalytix. K. Duffin: Employee; Current; Eli Lilly and Company. A. Krolewski: None.
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