Dulaglutide showed biomarker evidence of reducing kidney fibrosis (less new scar formation, more scar breakdown) compared to insulin in type 2 diabetes patients with chronic kidney disease.
Fibrosis reversed, not just slowedDulaglutide decreased new scar tissue formation (PRO-C6 down) while increasing scar breakdown (C3M up) — suggesting the GLP-1 drug may actively reverse kidney fibrosis, not just slow progression
What the researchers found
In this post-hoc analysis from the AWARD-7 trial, the GLP-1 agonist dulaglutide showed biomarker evidence of reducing kidney fibrosis compared to insulin glargine in type 2 diabetes patients with CKD. Specifically:
- Serum PRO-C6 (a marker of new scar tissue formation — type VI collagen) decreased with dulaglutide but increased with insulin glargine at both 26 and 52 weeks (p<0.01)
- Urine C3M (a marker of scar tissue breakdown — type III collagen degradation) increased with dulaglutide but decreased with insulin glargine (p<0.05)
This combination — less new fibrosis plus more scar tissue clearance — suggests dulaglutide may actively reverse kidney scarring, not just slow its progression. The effects were more pronounced in patients with macroalbuminuria (severe kidney damage). Both fibrosis biomarkers correlated with kidney function (eGFR), supporting their clinical relevance.
Why it matters
Kidney fibrosis (scarring) is the final common pathway to kidney failure — once enough scar tissue accumulates, the kidney can't function. Until now, we could slow fibrosis but couldn't reverse it. This study provides the first biomarker evidence that a GLP-1 agonist may actually reduce kidney scarring at the molecular level, not just slow kidney function decline. If confirmed, this adds a powerful mechanistic explanation for why GLP-1 drugs protect kidneys in trials like FLOW.
The numbers in context
N=330 analyzed · 52-week treatment · PRO-C6 (fibrosis): -4.6% dulaglutide vs +5.7% insulin (week 26, p<0.01) · C3M (scar breakdown): +10.9% dulaglutide vs -10.0% insulin (week 26, p<0.05) · Greater effects in macroalbuminuria subgroup · Both markers correlated with eGFR
How the study worked
This was an exploratory post-hoc analysis of the AWARD-7 randomized trial comparing dulaglutide 1.5 mg weekly to insulin glargine in 330 patients with type 2 diabetes and moderate-to-severe CKD. Two collagen-based fibrosis biomarkers were measured using ELISA assays: serum PRO-C6 (type VI collagen formation, reflecting new fibrosis) and urine C3M (type III collagen degradation, reflecting scar breakdown). Changes were analyzed using mixed-effects models and correlated with eGFR outcomes.
Who was studied
330 patients with type 2 diabetes and moderate-to-severe CKD from the AWARD-7 trial
What this study cannot tell us
This is a post-hoc exploratory analysis — the AWARD-7 trial was not designed to test kidney fibrosis as a primary outcome, so these findings are hypothesis-generating. The biomarkers are surrogate measures of fibrosis, not direct tissue measurements (which would require kidney biopsies). The comparison is against insulin glargine rather than placebo, making it unclear whether dulaglutide is reducing fibrosis or insulin is increasing it. The sample size of 330 is moderate for biomarker analyses.
How to read the evidence
This is a post-hoc exploratory analysis from a randomized trial, using surrogate biomarkers rather than direct tissue measurement. While the biomarker changes are statistically significant and biologically coherent, the exploratory nature and lack of kidney biopsy confirmation limit the evidence grade. The findings are hypothesis-generating and require prospective validation.
When this study was published
Published in 2023, this analysis is recent and contributes to the rapidly evolving understanding of how GLP-1 agonists protect kidneys. The FLOW trial results published subsequently have reinforced the kidney-protective class effect.
The bigger picture
The discovery that GLP-1 agonists may have anti-fibrotic effects on the kidney adds a new dimension to their already impressive benefit profile. Combined with cardiovascular protection, weight loss, and direct kidney function preservation shown in trials like FLOW, this fibrosis mechanism helps explain why GLP-1 drugs are emerging as transformative treatments for diabetic kidney disease. Anti-fibrotic kidney therapies have been a major unmet medical need — if GLP-1 drugs fill this gap, it would represent a significant advance.
Questions still open
- Would a study using kidney biopsy tissue confirm that the biomarker changes correspond to actual structural reduction in fibrosis?
- Do other GLP-1 agonists like semaglutide show the same anti-fibrotic biomarker changes?
- Is the anti-fibrotic effect a direct action of GLP-1 receptor activation on kidney cells, or an indirect result of improved glucose control and weight loss?
Common questions
Can GLP-1 drugs reverse kidney damage in diabetes?
What are kidney fibrosis biomarkers and why do they matter?
Read the original research
Indicators of Kidney Fibrosis in Patients with Type 2 Diabetes and Chronic Kidney Disease Treated with Dulaglutide.
American journal of nephrology, 54(1-2), 74-82
Citation
Tuttle, Katherine R; Wilson, Jonathan Matthew; Lin, Yanzhu; Qian, Hui-Rong; Genovese, Federica; Karsdal, Morten Asser; Duffin, Kevin L; Botros, Fady T. (2023). Indicators of Kidney Fibrosis in Patients with Type 2 Diabetes and Chronic Kidney Disease Treated with Dulaglutide.. American journal of nephrology, 54(1-2), 74-82. https://doi.org/10.1159/000529374