Kidney Week

Abstract: TH-PO1061

Trial Design and Baseline Characteristics from REMODEL: A Mechanistic Study of Semaglutide vs. Placebo in People with Type 2 Diabetes and CKD

Session Information

• CKD: Therapeutic Advances
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

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

David Cherney, MD, PhD

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

Petter Bjornstad, MD

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

Milenta Mariam Chacko, MSc

• Gunnarsson, Thomas P., Novo Nordisk A/S, Bagsvaerd, Hovedstaden, Denmark

Thomas P. Gunnarsson, PhD

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

Jeffrey B. Hodgin, MD, PhD

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

Matthias Kretzler, MD

• Belmar, Nicolas, Novo Nordisk A/S, Bagsvaerd, Hovedstaden, Denmark

Nicolas Belmar, MD, MSc

• Pruijm, Menno, Universite de Lausanne, Lausanne, Vaud, Switzerland

Menno Pruijm, MD

• Schytz, Philip Andreas, Novo Nordisk A/S, Bagsvaerd, Hovedstaden, Denmark

Philip Andreas Schytz, MD, PhD

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

Katherine R. Tuttle, MD, FASN

Background

Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD) and kidney failure globally. Semaglutide, a glucagon-like peptide-1 receptor agonist, reduces risks of major kidney, cardiovascular, and mortality outcomes in people with T2D and CKD as shown in the FLOW trial. Despite the clinical benefits, the precise kidney-specific mode-of-action (MoA) of semaglutide remains unclear.

Methods

REMODEL is a 52-week phase 3b trial investigating the kidney-specific MoA for semaglutide (once-weekly subcutaneous 1.0 mg) vs. placebo in people with T2D and CKD (Figure 1). Primary endpoints are magnetic-resonance imaging (MRI)-based measures of changes in kidney oxygenation, global kidney perfusion, inflammation and fibrosis. A subset of participants opted to undergo sequential kidney biopsies both at baseline and at the end of treatment for tissue-based interrogation including single nucleus transcriptomics, pathology, and morphometric examination.

Results

REMODEL enrolled 106 participants across 8 countries (Table 1). All participants were prescribed concomitant medications at baseline with 98.1% using RAAS inhibition, and 38.7% using SGLT2i. Baseline kidney biopsies were performed in 33 participants with characteristics similar to the entire cohort.

Conclusion

REMODEL will comprehensively assess multiple proposed physiological pathways for the kidney-specific MoA of semaglutide and will help elucidate kidney-specific benefits seen in the FLOW trial. The REMODEL trial has successfully enrolled a representative population of people with T2D and CKD, ensuring the generalizability and clinical relevance of the findings.

Funding

• Commercial Support – NOVO NORDISK AS