Dulaglutide Treatment in Patients with Type 2 Diabetes and Moderate-to-Severe CKD Improves Kidney Fibrosis Biomarker Levels
ASN Kidney Week
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 serum PRO-C6 (a marker for type VI collagen formation) are reported to correlate with CKD progression and lower eGFR.
This exploratory analysis evaluated changes in urinary C3M and serum PRO-C6 with dulaglutide 1.5 mg treatment as compared to insulin glargine in AWARD-7 in overall study population and the macroalbuminuria subgroup.
At baseline, the macroalbuminuria subgroup had numerically higher serum PRO-C6 levels and lower urinary C3M levels than the total population for both treatment groups. At baseline, both biomarker levels were comparable between treatment groups. At week 26 and 52 of treatment in the overall population, urinary C3M levels were significantly elevated and serum PRO-C6 levels were significantly reduced in the dulaglutide 1.5 mg group compared with insulin glargine group. These effects were consistent in participants with baseline macroalbuminuria (Table).
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.
Kidney & Diabetes
Tuttle, Katherine; Wilson, Jonathan Matthew; Lin, Yanzhu; Qian, Hui-Rong; Genovese, Federica; Karsdal, Morten Asser; Duffin, Kevin L.; and Botros, Fady T., "Dulaglutide Treatment in Patients with Type 2 Diabetes and Moderate-to-Severe CKD Improves Kidney Fibrosis Biomarker Levels" (2020). Articles, Abstracts, and Reports. 3762.