725-P: Protein Biomarkers Associated with Dulaglutide and Cardiovascular Events in REWIND

Abstract

In the REWIND trial, dulaglutide (DU) reduced the risk of CV outcomes compared with placebo (PL) (Major Adverse Cardiovascular Event [MACE]-3 hazard ratio 0.88) . This post hoc analysis studied circulating protein biomarkers associated with CV events to better understand how DU reduces CV risk. Patients ≥50 years of age with T2D, A1C ≤9.5%, BMI ≥23 kg/m2, and CV risk were treated DU (1.5 mg weekly) or PL. This case/control study matched 9 cases with MACE with 9 non-MACE controls. A total of protein biomarkers were measured by immunoassay in plasma and serum. Biomarkers associated with DU were first identified by fitting the natural log (ln) of biomarker changes from baseline to 2 years of treatment to an ANCOVA model; the p value cutoff was 0.0026 after Bonferroni correction. Then, the identified biomarkers were fit to a logistic regression model for MACE case/control to test possible impact on CV outcome. Four biomarkers were associated with DU: C-reactive protein (hsCRP) , N-terminal prohormone of brain natriuretic peptide (NT-proBNP) , and Growth/Differentiation Factor-15 (GDF-15) had attenuated increases over 2 years for DU vs. PL, and C-peptide had a greater increase over 2 years for DU vs. PL. Logistic regression analyses showed that patients with smaller increases in hsCRP, NT-proBNP, and GDF-15 were less likely to have MACE. C-peptide levels did not significantly impact MACE occurrence. Disclosure J.M.Wilson: Employee; Eli Lilly and Company. K.L.Duffin: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company, Pfizer Inc. H.C.Gerstein: Advisory Panel; Abbott, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Novo Nordisk, Pfizer Inc., Sanofi, Viatris Inc., Consultant; Kowa Company, Ltd., Other Relationship; DKSH, Eli Lilly and Company, Sanofi, Zuellig Pharma Holdings Pte. Ltd., Research Support; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. G.Pare: Advisory Panel; Amgen Inc., Bayer AG, Sanofi, Research Support; Bayer AG. S.Lee: None. H.M.Colhoun: Advisory Panel; Bayer AG, Eli Lilly and Company, Novo Nordisk, Consultant; AstraZeneca, Research Support; AstraZeneca, Stock/Shareholder; Bayer AG, Roche Pharmaceuticals. H.Qian: Employee; Eli Lilly and Company, Stock/Shareholder; Apple, Eli Lilly and Company. V.Pirro: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. A.Hoover: Employee; Eli Lilly and Company. M.Lakshmanan: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. G.Ruotolo: None. Funding Eli Lilly and Company