Phase 3 · Semaglutide

REMODEL trial results

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

Participants: 106
Status: completed
Completed: 2024-11-21
Sponsor: Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT04865770), updated at source Feb 10, 2026. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What REMODEL measured first

Change in Kidney Oxygenation (Cortex), Blood Oxygenation-level Dependent Magnetic Resonance Imaging (BOLD MRI) (R2*)Ratio of kidney oxygenation (cortex) · Baseline (week 0), End of treatment (week 52) · geometric mean

Measure	Semaglutide 1.0 mgn=71	Placebon=35
Bilateral cortex	0.98(5.35)	1.00(7.39)
Right cortex	0.98(5.65)	0.99(7.26)
Left cortex	0.98(7.51)	1.01(9.12)

Change in Kidney Oxygenation (Medulla), BOLD MRI (R2*)Ratio of kidney oxygenation (medulla) · Baseline (week 0), End of treatment (week 52) · geometric mean

Measure	Semaglutide 1.0 mgn=71	Placebon=35
Bilateral medulla	0.99(8.97)	1.01(11.37)
Right medulla	0.98(10.09)	1.02(10.83)
Left medulla	0.99(10.25)	1.02(13.02)

Change in Global Kidney Perfusion (MRI)Ratio of global kidney perfusion · Baseline (week 0), End of treatment (week 52) · geometric mean

Measure	Semaglutide 1.0 mgn=71	Placebon=35
Bilateral kidney	1.03(26.43)	0.99(24.39)
Right kidney	1.04(27.84)	0.98(28.85)
Left kidney	1.02(29.25)	1.01(26.83)

Change in Kidney Inflammation (Cortex), Longitudinal Relaxation Time (T1) Mapping (MRI)Ratio of kidney inflammation (cortex) · Baseline (week 0), End of treatment (week 52) · geometric mean

Measure	Semaglutide 1.0 mgn=71	Placebon=35
Bilateral cortex	1.01(3.78)	1.01(5.43)
Right cortex	1.01(3.88)	1.01(5.57)
Left cortex	1.01(3.93)	1.01(5.71)

Change in Kidney Inflammation (Medulla), T1 Mapping (MRI)Ratio of kidney inflammation (medulla) · Baseline (week 0), End of treatment (week 52) · geometric mean

Measure	Semaglutide 1.0 mgn=71	Placebon=35
Bilateral medulla	1.00(3.56)	1.00(5.13)
Right medulla	1.00(3.90)	1.01(4.85)
Left medulla	1.00(3.69)	1.00(5.91)

Side effects by arm

Side effects in REMODEL

Percent of participants affected, Up to week 57. The most common events the registry lists.

Event	Semaglutide 1.0 mg	Placebo
Any serious event	19.7%	14.3%
Diarrhoea	5.6%	11.4%
Diabetic retinopathy	5.6%	5.7%
Nasopharyngitis	0%	5.7%
Nausea	5.6%	5.7%
Upper respiratory tract infection	1.4%	5.7%
COVID-19	5.6%	0%
Decreased appetite	5.6%	0%

Secondary outcomes

What else it measured

Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy)log2 fold-change · Baseline (week 0), End of treatment (week 52) · number

Measure	Semaglutide 1.0 mg/Placebon=22
CNT-2, RSPO3	3.468216523
CNT-Immune, SLC8A1-AS1	2.8531071
EC-GC-1, KCNK6	-1.952545192
EC-GC-1, EMC10	-2.485824696
EC-GC-1, ENSG00000286145	1.831300888
EC-GC-1, LMF1	-1.528463786
EC-GC-1, ANKUB1	1.783402404
EC-GC-1, AHNAK	-1.368952211
EC-GC-1, ENSG00000286150	1.318309657
EC-GC-1, NSUN6	-1.464540152
EC-GC-1, TFCP2L1	-2.24516792
EC-GC-1, ENSG00000274422	-1.860725608

Change in Glomerular Basement Membrane Width (Kidney Biopsy)Nanometer (nm) · Baseline (week 0), End of treatment (week 52) · mean

Semaglutide 1.0 mgn=12	Placebon=9
-72.67(96.60)	-8.66(206.35)

Change in Apparent Diffusion Coefficient (ADC) (Cortex) (MRI)Ratio of ADC (cortex) · Baseline (week 0), End of treatment (week 52) · geometric mean

Measure	Semaglutide 1.0 mgn=71	Placebon=35
Bilateral cortex	1.00(6.56)	0.94(11.40)
Left cortex	1.01(8.50)	0.96(10.48)
Right cortex	0.98(6.70)	0.93(12.12)

Change in Apparent Diffusion Coefficient (ADC) (Medulla) (MRI)Ratio of ADC (medulla) · Baseline (week 0), End of treatment (week 52) · geometric mean

Measure	Semaglutide 1.0 mgn=71	Placebon=35
Bilateral medulla	0.98(8.90)	0.94(13.51)
Left medulla	0.99(9.51)	0.95(13.41)
Right medulla	0.98(10.00)	0.93(13.94)

Change in Mean Renal Artery Resistive Index (RARI) (MRI)Ratio of RARI · Baseline (week 0), End of treatment (week 52) · geometric mean

Measure	Semaglutide 1.0 mgn=71	Placebon=35
Bilateral renalartery	0.97(7.00)	1.01(6.13)
Right renalartery	0.98(8.38)	1.01(8.62)
Left renalartery	0.97(7.44)	1.01(6.43)

Change in Mean Arterial Flow (MRI)Ratio of mean arterial flow · Baseline (week 0), End of treatment (week 52) · geometric mean

Measure	Semaglutide 1.0 mgn=71	Placebon=35
Bilateral renalartery	0.96(24.96)	0.96(25.06)
Right renalartery	0.97(30.21)	0.95(29.09)
Left renalartery	0.96(25.06)	0.98(27.38)

Change in Natriuresis (Urinary Sodium Excretion) (Urinalysis)Millimoles per day (mmol/day) · Baseline (week 0), End of treatment (week 52) · mean

Semaglutide 1.0 mgn=57	Placebon=32
-7.3(71.3)	-26.9(85.2)

Change in Albumin Excretion Rate (Urinalysis)Milligrams per day (mg/d) · Baseline (week 0), End of treatment (week 52) · mean

Semaglutide 1.0 mgn=56	Placebon=33
-81.9(708.8)	-233.2(964.8)

Change in Kidney Function (Creatinine Clearance) (Urinalysis)Milliliter per minute · Baseline (week 0), End of treatment (week 52) · mean

Semaglutide 1.0 mgn=53	Placebon=33
3.8(26.6)	-12.6(34.2)

The trial

How REMODEL was run

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.

Semaglutide 1.0 mg OW: Once-weekly (OW) Semaglutide administered subcutaneously (s.c., under the skin).
Placebo (Semaglutide) 1.0 mg OW: Once-weekly (OW) placebo (Semaglutide) administered subcutaneously (s.c., under the skin).

Who could join the trial

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).

Published papers

Papers from REMODEL

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

GLPcompare is an informational data platform, not a medical provider or pharmacy. Nothing here is medical advice, a diagnosis, or a recommendation to start, stop, or change any treatment. Data is aggregated from public sources and can be incomplete or out of date. Always confirm with a licensed clinician and the current FDA label.