Kidney Week

Abstract: FR-OR089

Mechanistic Effects of Semaglutide on Kidney Disease in Type 2 Diabetes: The REMODEL Trial

Session Information

• Late-Breaking Research Orals - 2
  November 07, 2025 | Location: Grand Ballroom C, Convention Center
  Abstract Time: 04:42 PM - 04:54 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Tuttle, Katherine R., University of Washington, Seattle, Washington, United States

Katherine R. Tuttle, MD, FASN

• Bjornstad, Petter, University of Washington, Seattle, Washington, United States

Petter Bjornstad, MD

• Pruijm, Menno, Centre Hospitalier Universitaire Vaudois, Lausanne, VD, Switzerland

Menno Pruijm, MD

• Hodgin, Jeffrey B., University of Michigan, Ann Arbor, Michigan, United States

Jeffrey B. Hodgin, MD, PhD

• Cherney, David, University Health Network, Toronto, Ontario, Canada

David Cherney, MD, PhD

• Belmar, Nicolas, Novo Nordisk A/S, Søborg, Capital Region of Denmark, Denmark

Nicolas Belmar, MD, MS, MSc

• Chacko, Milenta Mariam, Novo Nordisk GBS, Bangalore, India

Milenta Mariam Chacko, MSc

• Das, Vivek, Novo Nordisk A/S, Søborg, Capital Region of Denmark, Denmark

Vivek Das, MSc, PhD

• Idorn, Thomas, Novo Nordisk A/S, Søborg, Capital Region of Denmark, Denmark

Thomas Idorn, MD, PhD

• Schytz, Philip Andreas, Novo Nordisk A/S, Søborg, Capital Region of Denmark, Denmark

Philip Andreas Schytz, MD, PhD

• Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States

Matthias Kretzler, MD

Background

Semaglutide reduces risks of losing kidney function and kidney failure in type 2 diabetes (T2D) with chronic kidney disease (CKD), yet the mechanisms remain unclear. The study aimed to discover the basis of kidney protection using a pathophysiologically integrative design combining functional magnetic resonance imaging with tissue-based analytics.

Methods

Adults with T2D, estimated glomerular filtration rate (eGFR) of 30-75 mL/min/1.73 m² and urinary albumin-to-creatinine ratio (UACR) 20-<5000 mg/g were randomized 2:1 to subcutaneous semaglutide 1.0 mg once-weekly or placebo for 52 weeks. A subgroup underwent paired kidney biopsy for histology, single-nuclear, and spatial transcriptomics.

Results

At baseline, participants (N=106) were 65 ±10 years old and 24% (n=25) were female. Mean eGFR was 51 ±10 mL/min/1.73m² and median UACR was 187 (interquartile range 60-546) mg/g. At 52 weeks, the mean estimated treatment effects for semaglutide versus placebo included 40% lower UACR and 12 mL/min higher creatinine clearance (Figure 1A). Perirenal and sinus fat volumes decreased by 25% and 13%, respectively, and the cortical apparent diffusion coefficient increased (estimated treatment ratio [ETR] 1.05, 95% CI 1.01-1.09) (Figure 1B). Semaglutide reduced the renal arterial resistive index (ETR 0.96, 0.93-0.99), while cortical oxygenation (ETR 0.98, 0.96-1.01) and perfusion (ETR 1.10, 0.98-1.24) trended higher (Figure 1C). In the biopsy subgroup (N=33), the arteriolar intimal area of the most diseased vessel decreased by 10%, and glomerular endothelial-cell transcriptomes revealed downregulation of genes in metabolic, inflammatory, and fibrotic pathways by semaglutide (Figure 1D).

Conclusion

In participants with T2D and CKD, semaglutide reduced kidney fat, improved glomerular hemodynamics, and ameliorated endothelial injury through metabolic reprogramming and mitigation of inflammation and fibrosis.

Funding

• Commercial Support – Novo Nordisk A/S

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025fdqxb4qe