Abstract: FR-PO0500
Retatrutide Increases Serum Uromodulin (UMOD) in People with Obesity with or Without Type 2 Diabetes and Without Kidney Disease
Session Information
- CKM: Clinical - Trials, Epidemiology, and Biomarkers
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 602 Cardiovascular-Kidney-Metabolic Health: Clinical
Authors
- Park, Yoson, Eli Lilly and Company, Indianapolis, Indiana, United States
- Titchenell, Paul M., Eli Lilly and Company, Indianapolis, Indiana, United States
- Matkovich, Scot J., Eli Lilly and Company, Indianapolis, Indiana, United States
- O'Dushlaine, Colm, Eli Lilly and Company, Indianapolis, Indiana, United States
- Thomas, Melissa K., Eli Lilly and Company, Indianapolis, Indiana, United States
- Badal, Shawn S., Eli Lilly and Company, Indianapolis, Indiana, United States
Background
Incretin receptor agonists have shown effects on eGFR and other kidney function measures in patients with and without CKD, and unimolecular multi-receptor agonists targeting GLP-1, GIP, and glucagon receptors are in clinical development for CKD. Retatrutide (Reta), a GLP-1R/GIPR/GCGR triple agonist, affected eGFR and urine albumin in two phase 2 trials of adults with obesity with or without T2D and without kidney disease. We perfomed an observational post-hoc proteomic analysis of these trials to identify circulating biomarkers in patients treated with Reta.
Methods
Serum proteins (Olink ExploreHT) were measured in a subset of subjects in two randomized, double-blind, placebo-controlled phase 2 trials: T2D trial (NCT04867785; N=281; Reta 0.5, 4, 8, 12 mg, dulaglutide 1.5 mg, or placebo; 36 wk) and obesity trial without T2D (NCT04881760; N=338; Reta 1, 4, 8, 12 mg or placebo; 48 wk). Relative percent change from baseline (PCBL) in fasting serum biomarkers was assessed by MMRM with FDR correction.
Results
Reta increased UMOD dose-dependently in both trials. In the T2D trial, Reta 12 mg raised UMOD +26.7% (95% CI: 16.0–37.3) at wk 36 (fdr=3.56e-5). In the obesity trial, Reta 12 mg raised UMOD +47.7% at wk 24 (fdr=3.35e-31) and +42.2% at wk 48 (95% CI 40.0–55.8; fdr=3.32e-22). Dulaglutide did not change UMOD (PCBL=−1.51%, 95% CI −9.31–6.96); placebo was unchanged at wk 24 (T2D PCBL=12.3%, fdr=0.47; Obesity PCBL=-0.66%, fdr=0.98) or at trial end. UMOD increases at 8 and 12 mg remains significant after adjusting for weight, HbA1c, or both. UMOD changes were accompanied by reported UACR reductions (baseline means 16.1 and 8.4 mg/g in T2D and obesity trials; up to −37% in T2D; −31.5% in obesity vs placebo) and dose-dependent eGFR increases in obesity cohort (baseline means 94.4 and 89.1 mL/min; up to +8.5 mL/min/1.73 m^2 with 12 mg).
Conclusion
In an observational biomarker correlation analysis of two phase 2 trials, Reta dose-dependently increased serum UMOD, correlating with previously reported kidney biomarker changes. Reduced circulating UMOD is linked to progression in patients with CKD in independent cohorts. Interestingly, UMOD and GCGR are co-expressed in Thick Ascending Limb Cells in human kidney scRNAseq studies. Mechanistic studies are needed to explore whether GCGR activation regulates UMOD levels and its relationship to kidney function.
Funding
- Commercial Support – Eli Lilly and Company