Indicators of Kidney Fibrosis in Patients with Type 2 Diabetes and Chronic Kidney Disease Treated with Dulaglutide.
American journal of nephrology
washington; spokane; Biomarkers; Diabetic kidney disease; Glucagon-like peptide-1 receptor agonists; Incretin therapy; Humans; Diabetes Mellitus, Type 2; Insulin Glargine; Hypoglycemic Agents; Collagen Type VI; Collagen Type III; Glycated Hemoglobin; Recombinant Fusion Proteins; Renal Insufficiency, Chronic; Biomarkers; Kidney
INTRODUCTION: In the AWARD-7 study in patients with type 2 diabetes and moderate-to-severe chronic kidney disease, once-weekly dulaglutide slowed the decline in estimated glomerular filtration rate (eGFR) and decreased the urine albumin/creatinine ratio compared to insulin glargine at the end of 52 weeks of treatment. In this exploratory post hoc analysis, changes in two fibrosis biomarkers, serum PRO-C6 (type VI collagen formation) and urine C3M (type III collagen degradation), were evaluated.
METHODS: In the groups treated with dulaglutide 1.5 mg or insulin glargine (N = 330), serum PRO-C6 and urine C3M were measured using competitive enzyme-linked immunosorbent assays. Biomarker changes were assessed by a mixed-effects model for repeated measures. Pearson correlation analyses were conducted to determine associations between changes in kidney fibrosis biomarkers and eGFR measures at 52 weeks.
RESULTS: At weeks 26 and 52 of treatment in the overall population, serum PRO-C6 levels were significantly lower in the dulaglutide group versus insulin glargine group with percent change from baseline of (least squares mean ± standard error) -4.6% ± 1.9 and -0.2% ± 2.2 versus 5.7% ± 2.0 and 8.0% ± 2.3 (p < 0.01), respectively, and urine C3M levels were significantly higher in the dulaglutide group versus insulin glargine group with percent change from baseline of 10.9% ± 8.2 and 20.7% ± 8.8 versus -10.0% ± 6.5 and -16.9% ± 6.4 (p < 0.05), respectively. These findings appeared greater in the subgroup with macroalbuminuria. Serum PRO-C6 negatively correlated with eGFR, while urine C3M positively correlated with eGFR.
CONCLUSION: Dulaglutide treatment was associated with biomarker changes that indicated lower type VI collagen formation and higher type III collagen degradation compared to treatment with insulin glargine, suggesting a potential drug effect to reduce kidney fibrosis.
Kidney & Diabetes
Tuttle, Katherine; Wilson, Jonathan Matthew; Lin, Yanzhu; Qian, Hui-Rong; Genovese, Federica; Karsdal, Morten Asser; Duffin, Kevin L; and Botros, Fady T, "Indicators of Kidney Fibrosis in Patients with Type 2 Diabetes and Chronic Kidney Disease Treated with Dulaglutide." (2023). Articles, Abstracts, and Reports. 7513.