Background: The drug combinations for rewriting trajectories of renal pathologies in type 2 diabetes (DC-ren) study focuses on DKD, a complication of diabetes often accompanied by cardiovascular disease. Novel biomarkers for identifying persons at increased risk of disease progression and predicting treatment response are currently needed. Levels of urinary C3M, a marker of type III collagen degradation, have been shown to correlate with CKD progression, and dulaglutide treatment improved levels of this biomarker compared with insulin glargine in persons with type 2 diabetes (T2D). We investigated the effect of combination therapy on urinary C3M in persons with T2D.

Method: We measured urinary C3M in urine collected at baseline and after years 1, 2, and 3 from 229 individuals with T2D enrolled in the DC-ren study. All persons were on renin-angiotensin system inhibitor (RASi) treatment at baseline and during follow-up. While some persons remained on RASi treatment (n = 184), others received glucagon-like peptide-1 receptor agonist (GLP-1 RA) on top of RASi (n = 45).

Results: The cohort consisted of 48% males (age of 66 ± 8 years and eGFR was 65 ± 17 ml/min/1.73 m2). Lower baseline levels of urinary C3M were associated with lower eGFR, and this relation remained consistent over time. Levels of urinary C3M were higher in persons after treatment with GLP-1 RA in combination with RASi compared to RASi alone (P = 0.034). In adjusted linear models (for the RASi group), an association of current urinary C3M with future eGFR was found (P < 0.01), indicating that urinary C3M is a prognostic risk marker for kidney function decline.

Conclusion: RASi in combination with GLP-1 RA treatment was associated with increased type III collagen degradation, suggesting a potential effect to reduce kidney fibrosis. This anti-fibrotic effect could be a mechanism for the beneficial effects observed with GLP-1 RA treatment on CKD in T2D.

Disclosure

A.Møller: None. S.Thöni: None. C.F.G.Laursen: None. M.A.Karsdal: Speaker's Bureau; Pfizer Inc. F.Genovese: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S. D.Rasmussen: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S.

© 2023 by the American Diabetes Association
2023
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