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Diabetes Mellitus, Type 2Phase 3REMODELNCT04865770

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)

A Phase 3 study testing Semaglutide in people with Diabetes Mellitus, Type 2 and Chronic Kidney Disease, run by Novo Nordisk A/S at 49 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Semaglutide
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
106 participants
Where
49 sitesin 8 countries
Study dates
28 Apr 2021to 21 Nov 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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).
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  • 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.

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

49 sites in 8 countries.

49 sites in 8 countries

United States20 sites

  • Atlanta Diabetes Associates

    Atlanta, Georgia, 30318

  • Emory University Hsptl - Atlanta

    Atlanta, Georgia, 30322

  • UC Anschutz Medical Campus

    Aurora, Colorado, 80045

  • Cleveland Clinic_Cleveland

    Cleveland, Ohio, 44195

  • Endeavor Health Glenbook Hosp

    Evanston, Illinois, 60201

  • North Suburban Nephrology LLC

    Gurnee, Illinois, 60031

  • Prolato Clinical Research Cntr

    Houston, Texas, 77054

  • Clinical Research Consultants, LLC

    Kansas City, Missouri, 64111

  • Academic Medical Research Institute

    Los Angeles, California, 90022

  • Medical College Of Wisconsin

    Milwaukee, Wisconsin, 53226

  • University of Minnesota Health Clinical

    Minneapolis, Minnesota, 55455

  • Roderick A. Comunale II MD Inc.

    National City, California, 91950

  • Advent Health-Res Inst

    Orlando, Florida, 32804

  • Sun Research Institute

    San Antonio, Texas, 78215

  • NE Clin Res of San Antonio

    San Antonio, Texas, 78233

  • University of Texas San Antonio

    San Antonio, Texas, 78284

  • N America Res Inst - San Dimas

    San Dimas, California, 91773

  • Univ of Washington Med Ctr

    Seattle, Washington, 98195

  • Providence Medical Research Center

    Spokane, Washington, 99204

  • University of Arizona-CaTs

    Tucson, Arizona, 85724

Other trials in United States

France6 sites

  • Centre Hospitalier Universitaire Amiens Picardie-Site Sud

    Amiens, 80054

  • Centre Hospitalier Universitaire de Rouen - Hopital de Bois Guillaume

    Bois-Guillaume, 76230

  • Centre Hospitalier Universitaire Grenoble Alpes-Site Nord Michallon-2

    Grenoble - Cédex 09, 38043

  • Les Hopitaux de Chartres-Hopital Louis Pasteur

    Le Coudray, 28630

  • Chu de Reims-Hopital Maison Blanche

    Reims, 51092

  • Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil

    Toulouse, 31059

Other trials in France

Italy5 sites

  • Azienda Ospedaliera Papa Giovanni XXIII

    Bergamo, 24127

  • Istituto Scientifico San Raffaele

    Milan, MI, 20132

  • Azienda Ospedaliera di Padova Clin.Med.3

    Padova, 35128

  • Presidio Ospedaliero Cisanello

    Pisa, 56124

  • Azienda Ospedaliero - Universitaria Sant'Andrea

    Roma, 00189

Other trials in Italy

Poland5 sites

  • In-Vivo Sp. z o.o.

    Bydgoszcz, 85-048

  • Centrum Medyczne "Diabetika"

    Radom, 26-600

  • Uniwersytecki Szpital Kliniczny Nr 2 PUM W Szczecinie

    Szczecin, 70-111

  • Miedzyleski Szpital Specjalistyczny, Oddzial Nefrologiczny

    Warsaw, 04-749

  • Prywatny Gabinet Janusz Gumprecht

    Zabrze, 41-800

Other trials in Poland

South Africa4 sites

  • Prof Rayner_Division of Nephrology

    Cape Town, Western Cape, 7925

  • Maxwell Centre

    Durban, KwaZulu-Natal, 4001

  • Precise Clinical Solutions (Pty) Ltd

    Durban, KwaZulu-Natal, 4092

  • Lenmed Shifa Private Hospital

    Durban, KwaZulu-Natal, 4901

Other trials in South Africa

Spain4 sites

  • Hospital Vall d'Hebron

    Barcelona, 08035

  • Hospital de Bellvitge

    L'Hospitalet de Llobregat, 08907

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

  • Hospital Clínico Universitario de Valencia

    Valencia, 46010

Other trials in Spain

Denmark3 sites

  • Nefrologisk Klinik P 2132

    Copenhagen, 2100

  • Rigshospitalet - Nefrologisk Klinik P 2132

    Copenhagen, 2100

  • Steno Diabetes Center Copenhagen

    Herlev, 2730

Other trials in Denmark

Canada2 sites

  • LMC ClinRsrh Inc.Brampton

    Brampton, Ontario, L6S 0C6

  • UHN-Toronto General Hospital

    Toronto, Ontario, M5G 2N2

Other trials in Canada

About this study

Official title: 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.

Read more

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.

Being tested
Semaglutide, Placebo (Semaglutide)
Medical subject headings
Diabetes Mellitus, Type 2, Renal Insufficiency, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SemaglutideDrug

    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 (Semaglutide)Drug

    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.

Study groups in NCT04865770
Study groupRoleWhat they receive
Semaglutide 1.0 mg OWExperimentalOnce-weekly (OW) Semaglutide administered subcutaneously (s.c., under the skin).
Receives: Drug: Semaglutide
Placebo (Semaglutide) 1.0 mg OWPlacebo comparatorOnce-weekly (OW) placebo (Semaglutide) administered subcutaneously (s.c., under the skin).
Receives: Drug: Placebo (Semaglutide)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline (week 0), End of treatment (week 52)

  2. 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.

    Measured: Baseline (week 0), End of treatment (week 52)

  3. 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.

    Measured: Baseline (week 0), End of treatment (week 52)

  4. 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.

    Measured: Baseline (week 0), End of treatment (week 52)

  5. 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.

    Measured: Baseline (week 0), End of treatment (week 52)

Secondary outcomes (9)

  1. 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.

    Measured: Baseline (week 0), End of treatment (week 52)

  2. 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.

    Measured: Baseline (week 0), End of treatment (week 52)

  3. 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.

    Measured: Baseline (week 0), End of treatment (week 52)

  4. 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.

    Measured: Baseline (week 0), End of treatment (week 52)

  5. 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.

    Measured: Baseline (week 0), End of treatment (week 52)

  6. 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.

    Measured: Baseline (week 0), End of treatment (week 52)

  7. 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.

    Measured: Baseline (week 0), End of treatment (week 52)

  8. Change in Albumin Excretion Rate (Urinalysis)

    Change in albumin excretion rate (urinalysis) from baseline (week 0) to end of treatment (week 52) is presented.

    Measured: Baseline (week 0), End of treatment (week 52)

  9. 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.

    Measured: Baseline (week 0), End of treatment (week 52)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Apr 2021
  2. Study start28 Apr 2021
  3. Primary completion21 Nov 2024
  4. Study completion21 Nov 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
106 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04865770
Sponsor's protocol ID
NN9535-4662
Other IDs
U1111-1248-7912, 2020-000828-19
Acronym
REMODEL
Status last verified
Feb 2026
First submitted
26 Apr 2021
Last updated
10 Feb 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Publications

  • Tuttle KR, Bjornstad P, Smith C, Pruijm M, McCown PJ, Hodgin JB, Cherney DZI, Belmar N, Chacko MM, Das V, Gunnarsson TP, Idorn T, Schytz PA, Zaratiegui A, Kretzler M. Effects of semaglutide on kidney disease in type 2 diabetes: a randomized placebo-controlled trial. Nat Med. 2026 Oct 1. doi: 10.1038/s41591-026-04674-2. Online ahead of print.

    PubMed 42823485

  • 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.

    PubMed 41207620

  • 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.

    PubMed 39963952

  • 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. 2025 Feb 1;20(2):159-168. doi: 10.2215/CJN.0000000584. Epub 2024 Oct 8.

    PubMed 39480988

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Semaglutide in people with Diabetes Mellitus, Type 2 and Chronic Kidney Disease, run by Novo Nordisk A/S at 49 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United States, France, Italy, Poland, South Africa and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Kidney Oxygenation (Cortex), Blood Oxygenation-level Dependent Magnetic Resonance Imaging (BOLD MRI) (R2*) (time frame: Baseline (week 0), End of treatment (week 52)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04865770, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2026; AzTrials last refreshed its copy on 6 Nov 2026.

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