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)

NCT04865770 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: NN9535-4662U1111-1248-79122020-000828-19
• Study Type: interventional
• Target: 106
• Locations: 8 countries
• Sites: 49

Brief 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. 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.

Conditions

Diabetes Mellitus, Type 2; Chronic Kidney Disease

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (9)

• Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy)

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

• Change in Glomerular Basement Membrane Width (Kidney Biopsy)

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

• Change in Apparent Diffusion Coefficient (ADC) (Cortex) (MRI)

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

• Change in Apparent Diffusion Coefficient (ADC) (Medulla) (MRI)

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

• Change in Mean Renal Artery Resistive Index (RARI) (MRI)

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

Study Arms (2)

Semaglutide 1.0 mg OW

EXPERIMENTAL

Once-weekly (OW) Semaglutide administered subcutaneously (s.c., under the skin).

Drug: Semaglutide

Placebo (Semaglutide) 1.0 mg OW

PLACEBO COMPARATOR

Once-weekly (OW) placebo (Semaglutide) administered subcutaneously (s.c., under the skin).

Drug: Placebo (Semaglutide)

Interventions

Semaglutide DRUG

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.

Semaglutide 1.0 mg OW

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.

Placebo (Semaglutide) 1.0 mg OW

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (49)

University of Arizona-CaTs

Tucson, Arizona, 85724, United States

Location

Academic Medical Research Institute

Los Angeles, California, 90022, United States

Location

Roderick A. Comunale II MD Inc.

National City, California, 91950, United States

Location

N America Res Inst - San Dimas

San Dimas, California, 91773, United States

Location

UC Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Advent Health-Res Inst

Orlando, Florida, 32804, United States

Location

Atlanta Diabetes Associates

Atlanta, Georgia, 30318, United States

Location

Emory University Hsptl - Atlanta

Atlanta, Georgia, 30322, United States

Location

Endeavor Health Glenbook Hosp

Evanston, Illinois, 60201, United States

Location

North Suburban Nephrology LLC

Gurnee, Illinois, 60031, United States

Location

University of Minnesota Health Clinical

Minneapolis, Minnesota, 55455, United States

Location

Clinical Research Consultants, LLC

Kansas City, Missouri, 64111, United States

Location

Cleveland Clinic_Cleveland

Cleveland, Ohio, 44195, United States

Location

Prolato Clinical Research Cntr

Houston, Texas, 77054, United States

Location

Sun Research Institute

San Antonio, Texas, 78215, United States

Location

NE Clin Res of San Antonio

San Antonio, Texas, 78233, United States

Location

University of Texas San Antonio

San Antonio, Texas, 78284, United States

Location

Univ of Washington Med Ctr

Seattle, Washington, 98195, United States

Location

Providence Medical Research Center

Spokane, Washington, 99204, United States

Location

Medical College Of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

LMC ClinRsrh Inc.Brampton

Brampton, Ontario, L6S 0C6, Canada

Location

UHN-Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

Nefrologisk Klinik P 2132

Copenhagen, 2100, Denmark

Location

Rigshospitalet - Nefrologisk Klinik P 2132

Copenhagen, 2100, Denmark

Location

Steno Diabetes Center Copenhagen

Herlev, 2730, Denmark

Location

Centre Hospitalier Universitaire Amiens Picardie-Site Sud

Amiens, 80054, France

Location

Centre Hospitalier Universitaire de Rouen - Hopital de Bois Guillaume

Bois-Guillaume, 76230, France

Location

Centre Hospitalier Universitaire Grenoble Alpes-Site Nord Michallon-2

Grenoble - Cédex 09, 38043, France

Location

Les Hopitaux de Chartres-Hopital Louis Pasteur

Le Coudray, 28630, France

Location

Chu de Reims-Hopital Maison Blanche

Reims, 51092, France

Location

Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil

Toulouse, 31059, France

Location

Istituto Scientifico San Raffaele

Milan, MI, 20132, Italy

Location

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Azienda Ospedaliera di Padova Clin.Med.3

Padua, 35128, Italy

Location

Presidio Ospedaliero Cisanello

Pisa, 56124, Italy

Location

Azienda Ospedaliero - Universitaria Sant'Andrea

Roma, 00189, Italy

Location

In-Vivo Sp. z o.o.

Bydgoszcz, 85-048, Poland

Location

Centrum Medyczne "Diabetika"

Radom, 26-600, Poland

Location

Uniwersytecki Szpital Kliniczny Nr 2 PUM W Szczecinie

Szczecin, 70-111, Poland

Location

Miedzyleski Szpital Specjalistyczny, Oddzial Nefrologiczny

Warsaw, 04-749, Poland

Location

Prywatny Gabinet Janusz Gumprecht

Zabrze, 41-800, Poland

Location

Maxwell Centre

Durban, KwaZulu-Natal, 4001, South Africa

Location

Precise Clinical Solutions (Pty) Ltd

Durban, KwaZulu-Natal, 4092, South Africa

Location

Lenmed Shifa Private Hospital

Durban, KwaZulu-Natal, 4901, South Africa

Location

Prof Rayner_Division of Nephrology

Cape Town, Western Cape, 7925, South Africa

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital de Bellvitge

L'Hospitalet de Llobregat, 08907, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Related Publications (3)

• 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.

  PMID: 41207620 DERIVED

• 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.

  PMID: 39963952 DERIVED

• 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.

  PMID: 39480988 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Renal Insufficiency, Chronic

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Clinical Reporting Office (2834)
• Organization: Novo Nordisk A/S

clinicaltrials@novonordisk.com

(+1) 866-867-7178

Study Officials

• Clinical Transparency (Dept.2834)

  Novo Nordisk A/S

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sponsor staff involved in the clinical trial is masked according to company standard procedures.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2021
• First Posted: April 29, 2021
• Study Start: April 28, 2021
• Primary Completion: November 21, 2024
• Study Completion: November 21, 2024
• Last Updated: February 10, 2026
• Results First Posted: January 14, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

DK (3); US (20); IT (5); PL (5); ZA (4); FR (6); CA (2); ES (4)