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)

NCT ID: NCT04865770

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-28
• Study Completion Date: 2024-11-21

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Semaglutide 1.0 mg OW

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

Group Type: EXPERIMENTAL

Semaglutide

Intervention Type: 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.

Placebo (Semaglutide) 1.0 mg OW

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

Group Type: PLACEBO_COMPARATOR

Placebo (Semaglutide)

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Transparency (Dept.2834)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

University of Arizona-CaTs

Tucson, Arizona, United States

Academic Medical Research Institute

Los Angeles, California, United States

N America Res Inst - San Dimas

San Dimas, California, United States

UC Anschutz Medical Campus

Aurora, Colorado, United States

Advent Health-Res Inst

Orlando, Florida, United States

Clinical Research Consultants, LLC

Kansas City, Missouri, United States

Prolato Clinical Research Cntr

Houston, Texas, United States

Sun Research Institute

San Antonio, Texas, United States

NE Clin Res of San Antonio

San Antonio, Texas, United States

Univ of Washington Med Ctr

Seattle, Washington, United States

Providence Medical Research Center

Spokane, Washington, United States

UHN-Toronto General Hospital

Toronto, Ontario, Canada

Nefrologisk Klinik P 2132

Copenhagen, , Denmark

Rigshospitalet - Nefrologisk Klinik P 2132

Copenhagen, , Denmark

Steno Diabetes Center Copenhagen

Herlev, , Denmark

Centre Hospitalier Universitaire Amiens Picardie-Site Sud

Amiens, , France

Centre Hospitalier Universitaire de Rouen - Hopital de Bois Guillaume

Bois-Guillaume, , France

Centre Hospitalier Universitaire Grenoble Alpes-Site Nord Michallon-2

Grenoble - Cédex 09, , France

Chu de Reims-Hopital Maison Blanche

Reims, , France

Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil

Toulouse, , France

Istituto Scientifico San Raffaele

Milan, MI, Italy

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, , Italy

Azienda Ospedaliera di Padova Clin.Med.3

Padua, , Italy

Azienda Ospedaliero - Universitaria Sant'Andrea

Roma, , Italy

In-Vivo Sp. z o.o.

Bydgoszcz, , Poland

Centrum Medyczne "Diabetika"

Radom, , Poland

Uniwersytecki Szpital Kliniczny Nr 2 PUM W Szczecinie

Szczecin, , Poland

Miedzyleski Szpital Specjalistyczny, Oddzial Nefrologiczny

Warsaw, , Poland

Prywatny Gabinet Janusz Gumprecht

Zabrze, , Poland

Maxwell Centre

Durban, KwaZulu-Natal, South Africa

Precise Clinical Solutions (Pty) Ltd

Durban, KwaZulu-Natal, South Africa

Lenmed Shifa Private Hospital

Durban, KwaZulu-Natal, South Africa

Prof Rayner_Division of Nephrology

Cape Town, Western Cape, South Africa

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital de Bellvitge

L'Hospitalet de Llobregat, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Countries

United States; Canada; Denmark; France; Italy; Poland; South Africa; Spain

References

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.

Reference Type: DERIVED

PMID: 41207620 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39963952 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39480988 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1248-7912

Identifier Type: OTHER

Identifier Source: secondary_id

2020-000828-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NN9535-4662

Identifier Type: -

Identifier Source: org_study_id