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Cited by 31Chronic Kidney Disease and DiabetesDiabetes Treatment and ManagementAcute Kidney Injury Research

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Indicators of Kidney Fibrosis in Patients with Type 2 Diabetes and Chronic Kidney Disease Treated with Dulaglutide

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Tuttle, Katherine R., Wilson, Jonathan Matthew, Lin, Yanzhu, Qian, Hui-Rong, Genovese, Federica, Karsdal, Morten Asser, Duffin, Kevin L., Botros, Fady T.·2023·American Journal of Nephrology
DOI 10.1159/000529374
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Abstract

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.

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  • A follow-up post hoc analysis identified improvements in fibrosis-related biomarkers in the dulaglutide group, including lower serum PRO-C6 levels for type VI collagen formation and higher urine C3M levels for type III collagen degradation.

    “A follow-up post hoc analysis identified improvements in fibrosis-related biomarkers in the dulaglutide group, including lower serum PRO-C6 levels for type VI collagen formation and higher urine C3M levels for type III collagen degradation (74).”

    From Antiinflammatory actions of glucagon-like peptide-1–based therapies beyond metabolic benefits (2025) · cites this paper as [74]

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Research works printed but not linked: 29

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Metadata

Authors
Tuttle, K. R., Wilson, J. M., Lin, Y., Qian, H.-R., Genovese, F., Karsdal, M. A., Duffin, K. L., & Botros, F. T.
Affiliations
  • University of Washington (US)
  • Eli Lilly (United States) (US)
  • Nordic Bioscience (Denmark) (DK)
ORCID
Venue
American Journal of Nephrology
Publisher
S. Karger AG
Published
2023
Volume
54
Issue
1-2
Pages
74-82
ISSN
  • 0250-8095 (ISSN-L)
  • 1421-9670
DOI
10.1159/000529374
OpenAlex
W4319456726
Cited by
31
References
0
Citations by year
2026: 11 · 2025: 10 · 2024: 7 · 2023: 3
FWCI
6.02
Type
journal article
Language
en
Open access
Licence
Locations
  • American Journal of Nephrology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Eli Lilly and Company (LY2189265)
  • National Institutes of Health (UL1TR002319)
  • National Heart, Lung, and Blood Institute (OT2HL161847)
  • National Institute of Diabetes and Digestive and Kidney Diseases (U2CDK114886, U54DK083912, U01DK100846)
  • National Center for Advancing Translational Sciences
  • National Institute on Minority Health and Health Disparities (R01MD014712)
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
Keywords
dulaglutide, renal fibrosis, type 2 diabetes, chronic kidney disease, PRO-C6, collagen VI, C3M, estimated glomerular filtration rate, insulin glargine, GLP-1 receptor agonists, macroalbuminuria
MeSH terms
Insulin Glargine, Diabetes Mellitus, Type 2, Glucagon-Like Peptides, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Immunoglobulin Fc Fragments, Kidney, Recombinant Fusion Proteins, Biomarkers, Collagen Type III, Collagen Type VI, Renal Insufficiency, Chronic

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