Dulaglutide improves kidney fibrosis biomarker levels in patients with type 2 diabetes and moderate-to-severe chronic kidney disease

The AWARD-7 clinical trial demonstrated that once-weekly dulaglutide slowed the decline in estimated glomerular filtration rate (eGFR) and decreased urine albumin/creatinine ratio compared to insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (CKD). Lower levels of urinary C3M, a marker for type III collagen degradation, and increased level of plasma PRO-C6, a marker for type VI collagen formation, have been reported to correlate with CKD progression and lower eGFR. This exploratory analysis evaluated changes in urinary C3M and plasma PRO-C6 in response to treatment with dulaglutide 1.5 mg compared to insulin glargine in AWARD-7. At baseline, urinary C3M and serum PRO-C6 levels were comparable between the dulaglutide 1.5 mg and insulin glargine groups. At week 26 and 52 of treatment, urinary C3M levels were significantly higher and serum PRO-C6 levels were significantly lower in the dulaglutide 1.5 mg group compared with insulin glargine group, respectively (Table). In conclusion, dulaglutide was associated with decreased levels of biomarkers for type VI collagen formation and increased type III collagen degradation, suggesting a potential effect to reduce kidney fibrosis. These anti-fibrotic effects could be a potential mechanism for the beneficial effects observed with dulaglutide treatment on CKD in type 2 diabetes. Disclosure K.R. Tuttle: Consultant; Self; AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Goldfinch Bio, Novo Nordisk Inc. J.M. Wilson: Employee; Self; Lilly Diabetes. Y. Lin: None. H. Qian: Employee; Self; Eli Lilly and Company. K. Kelly-Boruff: Employee; Self; Eli Lilly and Company. F. Genovese: None. M.A. Karsdal: Stock/Shareholder; Self; Nordic Bioscience. K.L. Duffin: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Pfizer Inc. F.T. Botros: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Funding Eli Lilly and Company