A Research Study to Find Out How Semaglutide Works in the Kidneys Compared to Placebo, in People With Type 2 Diabetes and Chronic Kidney Disease (the REMODEL Trial) (REMODEL)

Renal Mode of Action of Semaglutide in Patients With Type 2 Diabetes and Chronic Kidney Disease

We are doing this study to learn more about how semaglutide may help fight chronic kidney disease in people with type 2 diabetes. We are doing this by looking into how semaglutide works in the kidneys.

Participants will either get semaglutide or placebo (a 'dummy' medicine) - which treatment participants get is decided by chance.

Semaglutide is a medicine doctors can prescribe in some countries for the treatment of type 2 diabetes.

Participants will get the study medicine in a pen. Participants will use the pen to inject the medicine into the skin once a week.

The study will last for about 1 year. Participants will have 11 visits to the clinic, and 2 phone visits. Some of the visits could be in different locations.

Study staff will take blood samples at most of these visits. At 9 visits, participants will be asked to bring a sample of their first morning urine. At 4 of the visits participants will have to bring urine that they have collected over the last 24 hours.

The study includes magnetic resonance imaging (MRI) scans of participants' kidneys which is a test that shows a detailed picture of organs and other parts inside the body. The scan will last for 30 minutes, and is free of radiation.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Chronic Kidney Disease
• Intervention / Treatment: Drug: Semaglutide; Drug: Placebo (Semaglutide)

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6S 0C6
      • LMC ClinRsrh Inc.Brampton
    • Toronto, Ontario, Canada, M5G 2N2
      • UHN-Toronto General Hospital
• Denmark
  • Copenhagen, Denmark, 2100
    • Nefrologisk Klinik P 2132
  • Copenhagen, Denmark, 2100
    • Rigshospitalet - Nefrologisk Klinik P 2132
  • Herlev, Denmark, 2730
    • Steno Diabetes Center Copenhagen
• France
  • Amiens, France, 80054
    • Centre Hospitalier Universitaire Amiens Picardie-Site Sud
  • Bois-Guillaume, France, 76230
    • Centre Hospitalier Universitaire de Rouen - Hopital de Bois Guillaume
  • Grenoble - Cédex 09, France, 38043
    • Centre Hospitalier Universitaire Grenoble Alpes-Site Nord Michallon-2
  • Le Coudray, France, 28630
    • Les Hopitaux de Chartres-Hopital Louis Pasteur
  • Reims, France, 51092
    • Chu de Reims-Hopital Maison Blanche
  • Toulouse, France, 31059
    • Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil
• Italy
  • Bergamo, Italy, 24127
    • Azienda Ospedaliera Papa Giovanni XXIII
  • Padua, Italy, 35128
    • Azienda Ospedaliera di Padova Clin.Med.3
  • Pisa, Italy, 56124
    • Presidio Ospedaliero Cisanello
  • Roma, Italy, 00189
    • Azienda ospedaliero - universitaria Sant'Andrea
  • MI
    • Milan, MI, Italy, 20132
      • Istituto Scientifico San Raffaele
• Poland
  • Bydgoszcz, Poland, 85-048
    • In-Vivo Sp. z o.o.
  • Radom, Poland, 26-600
    • Centrum Medyczne "Diabetika"
  • Szczecin, Poland, 70-111
    • Uniwersytecki Szpital Kliniczny Nr 2 PUM w Szczecinie
  • Warsaw, Poland, 04-749
    • Miedzyleski Szpital Specjalistyczny, Oddzial Nefrologiczny
  • Zabrze, Poland, 41-800
    • Prywatny Gabinet Janusz Gumprecht
• South Africa
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4001
      • Maxwell Centre
    • Durban, KwaZulu-Natal, South Africa, 4092
      • Precise Clinical Solutions (Pty) Ltd
    • Durban, KwaZulu-Natal, South Africa, 4901
      • Lenmed Shifa Private Hospital
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7925
      • Prof Rayner_Division of Nephrology
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • L'Hospitalet de Llobregat, Spain, 08907
    • Hospital De Bellvitge
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona-CaTs
  • California
    • Los Angeles, California, United States, 90022
      • Academic Medical Research Institute
    • National City, California, United States, 91950
      • Roderick A. Comunale II MD Inc.
    • San Dimas, California, United States, 91773
      • N America Res Inst - San Dimas
  • Colorado
    • Aurora, Colorado, United States, 80045
      • UC Anschutz Medical Campus
  • Florida
    • Orlando, Florida, United States, 32804
      • Advent Health-Res Inst
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Atlanta Diabetes Associates
    • Atlanta, Georgia, United States, 30322
      • Emory University Hsptl - Atlanta
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Endeavor Health Glenbook Hosp
    • Gurnee, Illinois, United States, 60031
      • North Suburban Nephrology LLC
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Health Clinical
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Clinical Research Consultants, LLC
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic_Cleveland
  • Texas
    • Houston, Texas, United States, 77054
      • Prolato Clinical Research Cntr
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute
    • San Antonio, Texas, United States, 78233
      • NE Clin Res of San Antonio
    • San Antonio, Texas, United States, 78284
      • University of Texas San Antonio
  • Washington
    • Seattle, Washington, United States, 98195
      • Univ of Washington Med Ctr
    • Spokane, Washington, United States, 99204
      • Providence Medical Research Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female.
• Age above or equal to 18 years at the time of signing informed consent.
• Diagnosed with T2D (type 2 diabetes) greater than or equal to 180 days prior to the day of screening.
• HbA1c (glycated haemoglobin) below or equal to 9.0 percent (below or equal to 75 mmol/mol).

• Depending on biopsy/non-biopsy population:

  1. For subjects in the non-biopsy population: Serum creatinine-based eGFR greater than or equal to 30 and below or equal to 75 mL/min/1.73 m^2(CKD-EPI).
  2. For subjects in the biopsy sub-population: Serum creatinine-based eGFR greater than or equal to 40 and below or equal to 75 mL/min/1.73 m^2(CKD-EPI).
• UACR ( Urinary albumin-to-creatinine ratio ) greater than or equal to 20 and below 5000 mg/g.
• Treatment with maximum labelled or tolerated dose of a renin-angiotensin-aldosterone system (RAAS) blocking agent including an angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB)) unless such treatment is contraindicated or not tolerated.Treatment dose must be stable for at least 28 days prior to screening.

Exclusion Criteria:

• Use of any glucagon-like peptide 1 receptor agonist (GLP-1 RA) within 30 days prior to screening.
• A prior solid organ transplant or awaiting solid organ transplant.
• Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening.
• Presence or history of malignant neoplasms (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) within 5 years prior to the day of screening.
• Congenital or hereditary kidney diseases including polycystic kidney disease, autoimmune kidney diseases including glomerulonephritis or congenital urinary tract malformations.
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and Visit 2. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
• Treatment with systemic anti-inflammatory or immunosuppressant drugs within 90 days prior to screening. Stable treatment with acetylsalicylic acid for prevention of cardiovascular events and occasional use of propionic acid derivatives drugs (e.g. ibuprofen) is allowed.
• Any contraindication for MRI according to standard checklist used in clinical routine, including claustrophobia or metallic foreign bodies, metallic implants, internal electrical devices, or permanent makeup/tattoos that cannot be declared MR compatible.
• Combination use of an ACE (angiotensin-converting enzyme) inhibitor and an ARB (angiotensin II receptor blockers).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide 1.0 mg OW; Once-weekly (OW) Semaglutide administered subcutaneously (s.c., under the skin).	Drug: Semaglutide; Semaglutide given subcutaneously (sc, under the skin) once weekly. Dose gradually increased over 8 weeks from 0.25 to 1.0 mg. The study will last for about 1 year.
Placebo Comparator: Placebo (Semaglutide) 1.0 mg OW; Once-weekly (OW) placebo (Semaglutide) administered subcutaneously (s.c., under the skin).	Drug: Placebo (Semaglutide); Placebo (Semaglutide) given subcutaneously (sc, under the skin) once weekly. Dose gradually increased over 8 weeks from 0.25 to 1.0 mg. The study will last for about 1 year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Kidney Oxygenation (Cortex), Blood Oxygenation-level Dependent Magnetic Resonance Imaging (BOLD MRI) (R2*)	Change in kidney oxygenation in cortex assessed by BOLD (blood oxygenation level dependent) MRI from baseline (week 0) to end of treatment (week 52) is presented. R2* is a measure used in BOLD MRI to indicate the level of tissue oxygenation. A higher R2* value means lower tissue oxygenation while a lower R2* value means higher tissue oxygenation.	Baseline (week 0), End of treatment (week 52)
Change in Kidney Oxygenation (Medulla), BOLD MRI (R2*)	Change in kidney oxygenation in medulla assessed by BOLD (blood oxygenation level dependent) MRI from baseline (week 0) to end of treatment (week 52) is presented. R2* is a measure used in BOLD MRI to indicate the level of tissue oxygenation. A higher R2* value means lower tissue oxygenation while a lower R2* value means higher tissue oxygenation.	Baseline (week 0), End of treatment (week 52)
Change in Global Kidney Perfusion (MRI)	Change in global kidney perfusion assessed by phase contrast MRI from baseline (week 0) to end of treatment (week 52) is presented.	Baseline (week 0), End of treatment (week 52)
Change in Kidney Inflammation (Cortex), Longitudinal Relaxation Time (T1) Mapping (MRI)	Change in kidney inflammation in cortex assessed by T1 mapping MRI from baseline (week 0) to end of treatment (week 52) is presented.	Baseline (week 0), End of treatment (week 52)
Change in Kidney Inflammation (Medulla), T1 Mapping (MRI)	Change in kidney inflammation in medulla assessed by T1 mapping MRI from baseline (week 0) to end of treatment (week 52) is presented.	Baseline (week 0), End of treatment (week 52)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy)	Changes in gene expression were assessed by single nucleus RNA sequencing (kidney biopsies) from baseline (week 0) to end of treatment (week 52). Cell type annotation was performed prior to the analysis. The analysis reports the log2 fold change in form of differential gene expression per cell type from baseline, comparing treatment arms. Genes are considered significant if fold change > 0.5 or < 0.5 and false discovery rate (FDR) <0.1; these criteria help identify biologically significant genes that are reliably differentially expressed in patients with conditions such as Type 2 diabetes and chronic kidney disease. The differential expression was estimated using a linear mixed model that included participant as a random effect. The cell types presented are those that contain these differentially expressed genes demonstrating the treatment response. This threshold is based on findings published in cross-sectional observational studies related to disease impact and gene activity.	Baseline (week 0), End of treatment (week 52)
Change in Glomerular Basement Membrane Width (Kidney Biopsy)	Change in glomerular basement membrane width assessed in kidney biopsy from baseline (week 0) to end of treatment (week 52) is presented.	Baseline (week 0), End of treatment (week 52)
Change in Apparent Diffusion Coefficient (ADC) (Cortex) (MRI)	Change in apparent diffusion coefficient in cortex assessed by MRI from baseline (week 0) to end of treatment (week 52) is presented.	Baseline (week 0), End of treatment (week 52)
Change in Apparent Diffusion Coefficient (ADC) (Medulla) (MRI)	Change in apparent diffusion coefficient in medulla assessed by MRI from baseline (week 0) to end of treatment (week 52) is presented.	Baseline (week 0), End of treatment (week 52)
Change in Mean Renal Artery Resistive Index (RARI) (MRI)	Change in renal arterial resistive index assessed by MRI from baseline (week 0) to end of treatment (week 52) is presented. RARI measures the preservation of blood flow in renal arteries throughout the cardiac cycle and is therefore a measure for resistance of blood flow within the renal arteries. It serves as an indicator of kidney vascular health and potential arterial stiffness or obstruction. It is prognostic for primary cardiovascular and renal events in type 2 diabetes, where a lower RARI predicts a lower rate of events. RARI is calculated by relating the difference between blood flow at maximum velocity during the cardiac contraction phase (peak systolic velocity, PSV) and the speed at the end of the relaxation phase, at the point of minimal velocity (end diastolic velocity, EDV) with PSV, i.e., RARI = (PSV-EDV)/PSV.	Baseline (week 0), End of treatment (week 52)
Change in Mean Arterial Flow (MRI)	Change in mean arterial flow assessed by MRI from baseline (week 0) to end of treatment (week 52) is presented.	Baseline (week 0), End of treatment (week 52)
Change in Natriuresis (Urinary Sodium Excretion) (Urinalysis)	Change in natriuresis (urinary sodium excretion) (urinalysis) from baseline (week 0) to end of treatment (week 52) is presented.	Baseline (week 0), End of treatment (week 52)
Change in Albumin Excretion Rate (Urinalysis)	Change in albumin excretion rate (urinalysis) from baseline (week 0) to end of treatment (week 52) is presented.	Baseline (week 0), End of treatment (week 52)
Change in Kidney Function (Creatinine Clearance) (Urinalysis)	Change in kidney function (creatinine clearance) (urinalysis) from baseline (week 0) to end of treatment (week 52) is presented.	Baseline (week 0), End of treatment (week 52)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (Dept.2834), Novo Nordisk A/S

Publications and helpful links

General Publications

• Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.
• Pruijm M, Belmar N, Bjornstad P, Cherney DZI, Das V, Gunnarsson T, Hodgin JB, Schytz PA, Tuttle KR, Kretzler M. REMODELing mechanistic trials for kidney disease: a multimodal, tissue-centered approach to understand the renal mechanism of action of semaglutide. Kidney Int. 2026 Jan;109(1):6-16. doi: 10.1016/j.kint.2025.10.005. Epub 2025 Nov 7.
• Mendonca L, Moura H, Chaves PC, Neves JS, Ferreira JP. The Impact of Glucagon-Like Peptide-1 Receptor Agonists on Kidney Outcomes: A Meta-Analysis of Randomized Placebo-Controlled Trials. Clin J Am Soc Nephrol. 2024 Oct 8;20(2):159-68. doi: 10.2215/CJN.0000000584. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2021
• Primary Completion (Actual): November 21, 2024
• Study Completion (Actual): November 21, 2024

Study Registration Dates

• First Submitted: April 26, 2021
• First Submitted That Met QC Criteria: April 26, 2021
• First Posted (Actual): April 29, 2021

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Renal Insufficiency, Chronic; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; semaglutide
• Other Study ID Numbers: NN9535-4662; U1111-1248-7912 (Other Identifier: World Health Organization (WHO)); 2020-000828-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No