Chronic Kidney Disease, Diabetes Mellitus, Type 2
Conditions
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.
Interventions
DRUGSemaglutide
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.
DRUGPlacebo (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.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Kidney Oxygenation (Cortex), Blood Oxygenation-level Dependent Magnetic Resonance Imaging (BOLD MRI) (R2*) | Baseline (week 0), End of treatment (week 52) | 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. |
| Change in Kidney Oxygenation (Medulla), BOLD MRI (R2*) | Baseline (week 0), End of treatment (week 52) | 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. |
| Change in Global Kidney Perfusion (MRI) | Baseline (week 0), End of treatment (week 52) | Change in global kidney perfusion assessed by phase contrast MRI from baseline (week 0) to end of treatment (week 52) is presented. |
| Change in Kidney Inflammation (Cortex), Longitudinal Relaxation Time (T1) Mapping (MRI) | Baseline (week 0), End of treatment (week 52) | Change in kidney inflammation in cortex assessed by T1 mapping MRI from baseline (week 0) to end of treatment (week 52) is presented. |
| Change in Kidney Inflammation (Medulla), T1 Mapping (MRI) | Baseline (week 0), End of treatment (week 52) | Change in kidney inflammation in medulla assessed by T1 mapping MRI from baseline (week 0) to end of treatment (week 52) is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | Baseline (week 0), End of treatment (week 52) | 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. |
| Change in Glomerular Basement Membrane Width (Kidney Biopsy) | Baseline (week 0), End of treatment (week 52) | Change in glomerular basement membrane width assessed in kidney biopsy from baseline (week 0) to end of treatment (week 52) is presented. |
| Change in Apparent Diffusion Coefficient (ADC) (Cortex) (MRI) | Baseline (week 0), End of treatment (week 52) | Change in apparent diffusion coefficient in cortex assessed by MRI from baseline (week 0) to end of treatment (week 52) is presented. |
| Change in Apparent Diffusion Coefficient (ADC) (Medulla) (MRI) | Baseline (week 0), End of treatment (week 52) | Change in apparent diffusion coefficient in medulla assessed by MRI from baseline (week 0) to end of treatment (week 52) is presented. |
| Change in Mean Renal Artery Resistive Index (RARI) (MRI) | Baseline (week 0), End of treatment (week 52) | 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. |
| Change in Mean Arterial Flow (MRI) | Baseline (week 0), End of treatment (week 52) | Change in mean arterial flow assessed by MRI from baseline (week 0) to end of treatment (week 52) is presented. |
| Change in Natriuresis (Urinary Sodium Excretion) (Urinalysis) | Baseline (week 0), End of treatment (week 52) | Change in natriuresis (urinary sodium excretion) (urinalysis) from baseline (week 0) to end of treatment (week 52) is presented. |
| Change in Albumin Excretion Rate (Urinalysis) | Baseline (week 0), End of treatment (week 52) | Change in albumin excretion rate (urinalysis) from baseline (week 0) to end of treatment (week 52) is presented. |
| Change in Kidney Function (Creatinine Clearance) (Urinalysis) | Baseline (week 0), End of treatment (week 52) | Change in kidney function (creatinine clearance) (urinalysis) from baseline (week 0) to end of treatment (week 52) is presented. |
Countries
Canada, Denmark, France, Italy, Poland, South Africa, Spain, United States
Contacts
STUDY_DIRECTORClinical Transparency (Dept.2834)
Novo Nordisk A/S
Participant flow
Recruitment details
The trial was conducted at 31 sites in 8 countries.
Pre-assignment details
Participants were randomized in a 2:1 ratio to receive semaglutide or placebo, respectively. Both added to standard-of-care treatment.
Participants by arm
| Arm | Count |
|---|---|
| Semaglutide 1.0 mg Participants received once-weekly (OW) subcutaneous (s. c.) injection of semaglutide for 52 weeks. Participants received a dose of 0.25 milligrams (mg) from week 0 to week 4, then the dose was increased to 0.5 mg from week 4 to week 8. From week 8 to week 52, the dosage was 1.0 mg. | 71 |
| Placebo Participants received once-weekly (OW) subcutaneous injection (s. c.) of placebo matched for semaglutide for 52 weeks. | 35 |
| Total | 106 |
Baseline characteristics
| Characteristic | Placebo | Total | Semaglutide 1.0 mg |
|---|---|---|---|
| Age, Continuous | 65.1 Years STANDARD_DEVIATION 11.3 | 65.3 Years STANDARD_DEVIATION 9.9 | 65.4 Years STANDARD_DEVIATION 9.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 8 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 87 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 11 Participants | 7 Participants |
| Race/Ethnicity, Customized American Indian Or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 15 Participants | 11 Participants |
| Race/Ethnicity, Customized Black Or African American | 5 Participants | 10 Participants | 5 Participants |
| Race/Ethnicity, Customized Not Reported | 4 Participants | 10 Participants | 6 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 4 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 22 Participants | 65 Participants | 43 Participants |
| Sex: Female, Male Female | 9 Participants | 25 Participants | 16 Participants |
| Sex: Female, Male Male | 26 Participants | 81 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 71 | 1 / 35 |
| other Total, other adverse events | 15 / 71 | 11 / 35 |
| serious Total, serious adverse events | 14 / 71 | 5 / 35 |
Outcome results
Primary
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.
Time frame: Baseline (week 0), End of treatment (week 52)
Population: Full analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall number of participants analyzed= FAS. Number Analyzed= number of participants with available data for particular timepoint, for the respective arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 1.0 mg | Change in Global Kidney Perfusion (MRI) | Bilateral kidney | 1.03 Ratio of global kidney perfusion | Geometric Coefficient of Variation 26.43 |
| Semaglutide 1.0 mg | Change in Global Kidney Perfusion (MRI) | Right kidney | 1.04 Ratio of global kidney perfusion | Geometric Coefficient of Variation 27.84 |
| Semaglutide 1.0 mg | Change in Global Kidney Perfusion (MRI) | Left kidney | 1.02 Ratio of global kidney perfusion | Geometric Coefficient of Variation 29.25 |
| Placebo | Change in Global Kidney Perfusion (MRI) | Bilateral kidney | 0.99 Ratio of global kidney perfusion | Geometric Coefficient of Variation 24.39 |
| Placebo | Change in Global Kidney Perfusion (MRI) | Right kidney | 0.98 Ratio of global kidney perfusion | Geometric Coefficient of Variation 28.85 |
| Placebo | Change in Global Kidney Perfusion (MRI) | Left kidney | 1.01 Ratio of global kidney perfusion | Geometric Coefficient of Variation 26.83 |
Comparison: Bilateral kidney: Responses are analysed using an ANCOVA with actual treatment, region and the stratification factors as categorical effects and the baseline value as a covariate.p-value: 0.095895% CI: [0.98, 1.24]ANCOVA
Comparison: Right kidney: Responses are analysed using an ANCOVA with actual treatment, region and the stratification factors as categorical effects and the baseline value as a covariate.p-value: 0.014595% CI: [1.03, 1.33]ANCOVA
Comparison: Left kidney: Responses are analysed using an ANCOVA with actual treatment, region and the stratification factors as categorical effects and the baseline value as a covariate.p-value: 0.331195% CI: [0.94, 1.21]ANCOVA
Primary
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.
Time frame: Baseline (week 0), End of treatment (week 52)
Population: Full analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall number of participants analyzed= FAS. Number Analyzed= number of participants with available data for particular timepoint, for the respective arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 1.0 mg | Change in Kidney Inflammation (Cortex), Longitudinal Relaxation Time (T1) Mapping (MRI) | Bilateral cortex | 1.01 Ratio of kidney inflammation (cortex) | Geometric Coefficient of Variation 3.78 |
| Semaglutide 1.0 mg | Change in Kidney Inflammation (Cortex), Longitudinal Relaxation Time (T1) Mapping (MRI) | Right cortex | 1.01 Ratio of kidney inflammation (cortex) | Geometric Coefficient of Variation 3.88 |
| Semaglutide 1.0 mg | Change in Kidney Inflammation (Cortex), Longitudinal Relaxation Time (T1) Mapping (MRI) | Left cortex | 1.01 Ratio of kidney inflammation (cortex) | Geometric Coefficient of Variation 3.93 |
| Placebo | Change in Kidney Inflammation (Cortex), Longitudinal Relaxation Time (T1) Mapping (MRI) | Bilateral cortex | 1.01 Ratio of kidney inflammation (cortex) | Geometric Coefficient of Variation 5.43 |
| Placebo | Change in Kidney Inflammation (Cortex), Longitudinal Relaxation Time (T1) Mapping (MRI) | Right cortex | 1.01 Ratio of kidney inflammation (cortex) | Geometric Coefficient of Variation 5.57 |
| Placebo | Change in Kidney Inflammation (Cortex), Longitudinal Relaxation Time (T1) Mapping (MRI) | Left cortex | 1.01 Ratio of kidney inflammation (cortex) | Geometric Coefficient of Variation 5.71 |
Comparison: Bilateral cortex: Responses are analysed using an ANCOVA with actual treatment, region and the stratification factors as categorical effects and the baseline value as a covariate.p-value: 0.865195% CI: [0.98, 1.02]ANCOVA
Comparison: Right cortex: Responses are analysed using an ANCOVA with actual treatment, region and the stratification factors as categorical effects and the baseline value as a covariate.p-value: 0.72495% CI: [0.98, 1.02]ANCOVA
Comparison: Left cortex: Responses are analysed using an ANCOVA with actual treatment, region and the stratification factors as categorical effects and the baseline value as a covariate.p-value: 0.719595% CI: [0.98, 1.02]ANCOVA
Primary
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.
Time frame: Baseline (week 0), End of treatment (week 52)
Population: Full analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall number of participants analyzed= FAS. Number Analyzed= number of participants with available data for particular timepoint, for the respective arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 1.0 mg | Change in Kidney Inflammation (Medulla), T1 Mapping (MRI) | Bilateral medulla | 1.00 Ratio of kidney inflammation (medulla) | Geometric Coefficient of Variation 3.56 |
| Semaglutide 1.0 mg | Change in Kidney Inflammation (Medulla), T1 Mapping (MRI) | Right medulla | 1.00 Ratio of kidney inflammation (medulla) | Geometric Coefficient of Variation 3.9 |
| Semaglutide 1.0 mg | Change in Kidney Inflammation (Medulla), T1 Mapping (MRI) | Left medulla | 1.00 Ratio of kidney inflammation (medulla) | Geometric Coefficient of Variation 3.69 |
| Placebo | Change in Kidney Inflammation (Medulla), T1 Mapping (MRI) | Bilateral medulla | 1.00 Ratio of kidney inflammation (medulla) | Geometric Coefficient of Variation 5.13 |
| Placebo | Change in Kidney Inflammation (Medulla), T1 Mapping (MRI) | Right medulla | 1.01 Ratio of kidney inflammation (medulla) | Geometric Coefficient of Variation 4.85 |
| Placebo | Change in Kidney Inflammation (Medulla), T1 Mapping (MRI) | Left medulla | 1.00 Ratio of kidney inflammation (medulla) | Geometric Coefficient of Variation 5.91 |
Comparison: Bilateral medulla: Responses are analysed using an ANCOVA with actual treatment, region and the stratification factors as categorical effects and the baseline value as a covariate.p-value: 0.933595% CI: [0.98, 1.02]ANCOVA
Comparison: Right medulla: Responses are analysed using an ANCOVA with actual treatment, region and the stratification factors as categorical effects and the baseline value as a covariate.p-value: 0.651795% CI: [0.98, 1.01]ANCOVA
Comparison: Left medulla: Responses are analysed using an ANCOVA with actual treatment, region and the stratification factors as categorical effects and the baseline value as a covariate.p-value: 0.901795% CI: [0.98, 1.02]ANCOVA
Primary
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.
Time frame: Baseline (week 0), End of treatment (week 52)
Population: Full analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall number of participants analyzed= FAS. Number Analyzed= number of participants with available data for particular timepoint, for the respective arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 1.0 mg | Change in Kidney Oxygenation (Cortex), Blood Oxygenation-level Dependent Magnetic Resonance Imaging (BOLD MRI) (R2*) | Bilateral cortex | 0.98 Ratio of kidney oxygenation (cortex) | Geometric Coefficient of Variation 5.35 |
| Semaglutide 1.0 mg | Change in Kidney Oxygenation (Cortex), Blood Oxygenation-level Dependent Magnetic Resonance Imaging (BOLD MRI) (R2*) | Right cortex | 0.98 Ratio of kidney oxygenation (cortex) | Geometric Coefficient of Variation 5.65 |
| Semaglutide 1.0 mg | Change in Kidney Oxygenation (Cortex), Blood Oxygenation-level Dependent Magnetic Resonance Imaging (BOLD MRI) (R2*) | Left cortex | 0.98 Ratio of kidney oxygenation (cortex) | Geometric Coefficient of Variation 7.51 |
| Placebo | Change in Kidney Oxygenation (Cortex), Blood Oxygenation-level Dependent Magnetic Resonance Imaging (BOLD MRI) (R2*) | Bilateral cortex | 1.00 Ratio of kidney oxygenation (cortex) | Geometric Coefficient of Variation 7.39 |
| Placebo | Change in Kidney Oxygenation (Cortex), Blood Oxygenation-level Dependent Magnetic Resonance Imaging (BOLD MRI) (R2*) | Right cortex | 0.99 Ratio of kidney oxygenation (cortex) | Geometric Coefficient of Variation 7.26 |
| Placebo | Change in Kidney Oxygenation (Cortex), Blood Oxygenation-level Dependent Magnetic Resonance Imaging (BOLD MRI) (R2*) | Left cortex | 1.01 Ratio of kidney oxygenation (cortex) | Geometric Coefficient of Variation 9.12 |
Comparison: Bilateral cortex: Responses are analysed using an ANCOVA with actual treatment, region and the stratification factors as categorical effects and the baseline value as a covariate, on log scale.p-value: 0.133395% CI: [0.96, 1.01]ANCOVA
Comparison: Right cortex: Responses are analysed using an ANCOVA with actual treatment, region and the stratification factors as categorical effects and the baseline value as a covariate, on log scale.p-value: 0.248795% CI: [0.96, 1.01]ANCOVA
Comparison: Left cortex: Responses are analysed using an ANCOVA with actual treatment, region and the stratification factors as categorical effects and the baseline value as a covariate, on log scale.p-value: 0.090795% CI: [0.94, 1]ANCOVA
Primary
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.
Time frame: Baseline (week 0), End of treatment (week 52)
Population: Full analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall number of participants analyzed= FAS. Number Analyzed= number of participants with available data for particular timepoint, for the respective arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 1.0 mg | Change in Kidney Oxygenation (Medulla), BOLD MRI (R2*) | Bilateral medulla | 0.99 Ratio of kidney oxygenation (medulla) | Geometric Coefficient of Variation 8.97 |
| Semaglutide 1.0 mg | Change in Kidney Oxygenation (Medulla), BOLD MRI (R2*) | Right medulla | 0.98 Ratio of kidney oxygenation (medulla) | Geometric Coefficient of Variation 10.09 |
| Semaglutide 1.0 mg | Change in Kidney Oxygenation (Medulla), BOLD MRI (R2*) | Left medulla | 0.99 Ratio of kidney oxygenation (medulla) | Geometric Coefficient of Variation 10.25 |
| Placebo | Change in Kidney Oxygenation (Medulla), BOLD MRI (R2*) | Bilateral medulla | 1.01 Ratio of kidney oxygenation (medulla) | Geometric Coefficient of Variation 11.37 |
| Placebo | Change in Kidney Oxygenation (Medulla), BOLD MRI (R2*) | Right medulla | 1.02 Ratio of kidney oxygenation (medulla) | Geometric Coefficient of Variation 10.83 |
| Placebo | Change in Kidney Oxygenation (Medulla), BOLD MRI (R2*) | Left medulla | 1.02 Ratio of kidney oxygenation (medulla) | Geometric Coefficient of Variation 13.02 |
Comparison: Bilateral medulla: The responses are analysed using an ANCOVA with actual treatment, region and the stratification factors as categorical effects and the baseline value as a covariate.p-value: 0.561995% CI: [0.94, 1.03]ANCOVA
Comparison: Right medulla: The responses are analysed using an ANCOVA with actual treatment, region and the stratification factors as categorical effects and the baseline value as a covariate.p-value: 0.277495% CI: [0.93, 1.02]ANCOVA
Comparison: Left medulla: The responses are analysed using an ANCOVA with actual treatment, region and the stratification factors as categorical effects and the baseline value as a covariate.p-value: 0.792495% CI: [0.94, 1.04]ANCOVA
Secondary
Change in Albumin Excretion Rate (Urinalysis)
Change in albumin excretion rate (urinalysis) from baseline (week 0) to end of treatment (week 52) is presented.
Time frame: Baseline (week 0), End of treatment (week 52)
Population: Full analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall Number participants analyzed = number of participants with available data for particular timepoint, for the respective arms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 1.0 mg | Change in Albumin Excretion Rate (Urinalysis) | -81.9 Milligrams per day (mg/d) | Standard Deviation 708.8 |
| Placebo | Change in Albumin Excretion Rate (Urinalysis) | -233.2 Milligrams per day (mg/d) | Standard Deviation 964.8 |
Secondary
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.
Time frame: Baseline (week 0), End of treatment (week 52)
Population: Full analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall number of participants analyzed= FAS. Number Analyzed= number of participants with available data for particular timepoint, for the respective arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 1.0 mg | Change in Apparent Diffusion Coefficient (ADC) (Cortex) (MRI) | Bilateral cortex | 1.00 Ratio of ADC (cortex) | Geometric Coefficient of Variation 6.56 |
| Semaglutide 1.0 mg | Change in Apparent Diffusion Coefficient (ADC) (Cortex) (MRI) | Left cortex | 1.01 Ratio of ADC (cortex) | Geometric Coefficient of Variation 8.5 |
| Semaglutide 1.0 mg | Change in Apparent Diffusion Coefficient (ADC) (Cortex) (MRI) | Right cortex | 0.98 Ratio of ADC (cortex) | Geometric Coefficient of Variation 6.7 |
| Placebo | Change in Apparent Diffusion Coefficient (ADC) (Cortex) (MRI) | Bilateral cortex | 0.94 Ratio of ADC (cortex) | Geometric Coefficient of Variation 11.4 |
| Placebo | Change in Apparent Diffusion Coefficient (ADC) (Cortex) (MRI) | Left cortex | 0.96 Ratio of ADC (cortex) | Geometric Coefficient of Variation 10.48 |
| Placebo | Change in Apparent Diffusion Coefficient (ADC) (Cortex) (MRI) | Right cortex | 0.93 Ratio of ADC (cortex) | Geometric Coefficient of Variation 12.12 |
Secondary
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.
Time frame: Baseline (week 0), End of treatment (week 52)
Population: Full analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall number of participants analyzed= FAS. Number Analyzed= number of participants with available data for particular timepoint, for the respective arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 1.0 mg | Change in Apparent Diffusion Coefficient (ADC) (Medulla) (MRI) | Left medulla | 0.99 Ratio of ADC (medulla) | Geometric Coefficient of Variation 9.51 |
| Semaglutide 1.0 mg | Change in Apparent Diffusion Coefficient (ADC) (Medulla) (MRI) | Bilateral medulla | 0.98 Ratio of ADC (medulla) | Geometric Coefficient of Variation 8.9 |
| Semaglutide 1.0 mg | Change in Apparent Diffusion Coefficient (ADC) (Medulla) (MRI) | Right medulla | 0.98 Ratio of ADC (medulla) | Geometric Coefficient of Variation 10 |
| Placebo | Change in Apparent Diffusion Coefficient (ADC) (Medulla) (MRI) | Bilateral medulla | 0.94 Ratio of ADC (medulla) | Geometric Coefficient of Variation 13.51 |
| Placebo | Change in Apparent Diffusion Coefficient (ADC) (Medulla) (MRI) | Left medulla | 0.95 Ratio of ADC (medulla) | Geometric Coefficient of Variation 13.41 |
| Placebo | Change in Apparent Diffusion Coefficient (ADC) (Medulla) (MRI) | Right medulla | 0.93 Ratio of ADC (medulla) | Geometric Coefficient of Variation 13.94 |
Secondary
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.
Time frame: Baseline (week 0), End of treatment (week 52)
Population: Full analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall Number participants analyzed = number of participants with available data for particular timepoint, for the respective arms.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | CNT-2, RSPO3 | 3.468216523 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | CNT-Immune, SLC8A1-AS1 | 2.8531071 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, KCNK6 | -1.952545192 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, EMC10 | -2.485824696 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000286145 | 1.831300888 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, LMF1 | -1.528463786 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ANKUB1 | 1.783402404 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, AHNAK | -1.368952211 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000286150 | 1.318309657 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, NSUN6 | -1.464540152 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, TFCP2L1 | -2.24516792 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000274422 | -1.860725608 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, DPYD-AS1 | 1.996950045 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000248138 | 2.110414741 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ACSM2B | -1.785467699 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, CCNH | 1.033873239 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, QTRT1 | -2.415240141 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, CROCCP3 | -1.254541813 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000251034 | 1.750285729 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, LSAMP | -2.439268964 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, LHX1-DT | -4.256689925 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ESRRG | -1.527414037 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, CNTNAP2 | -2.377391827 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000284966 | 1.665764749 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, BICC1 | -1.445239386 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, GNA14-AS1 | 1.192645521 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, GUSBP11 | -1.318511642 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000233783 | 1.668536087 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, SEMA6A-AS1 | 1.183886707 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, RBMS3-AS2 | 1.572052032 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000286147 | -4.468841041 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, LINC00342 | -1.151143461 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, IRF3 | -1.566408786 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000249207 | 1.35685803 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, CRADD-AS1 | 1.972404772 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, TOX3 | -2.206055055 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000286458 | 1.271036656 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, SLC12A3 | -2.531722898 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, TALAM1 | 1.235573321 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, PCDH17 | 1.107442597 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ATP13A3 | 1.078246118 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000231772 | -2.382264501 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, FBXL19 | -2.166973377 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000254420 | 1.74612131 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, SPC25 | 1.329461228 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, SMAD4 | 1.13655744 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, UFM1 | 1.20264148 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000259564 | 2.071724947 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, SHOC1 | 1.634369451 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, MEF2C-AS2 | 1.753288691 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000285801 | 1.440844025 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, FAM228B | -1.22996414 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, GLS | 0.868999317 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, GDPD4 | -6.564026305 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, INSYN2A | 1.759769032 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, TNFRSF14 | -1.254004029 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, PRX | -1.199880651 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, PNN | -1.024604708 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, KCNQ1OT1 | -0.794847103 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ACAP3 | -1.44397269 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, BASP1-AS1 | -4.83539932 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, RBFOX1 | -1.706411849 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, CCDC90B-AS1 | -1.678217382 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000240499 | 1.514399208 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, LINC03076 | 1.545248095 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, LINC01409 | -1.022992954 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, CCT4 | 1.455396063 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, CDC73 | 0.802691458 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, NUMA1 | -0.931923316 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, FLT4 | -0.935590968 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, PDLIM5 | 0.764926487 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, SPCS3 | 1.02068757 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000250646 | 1.917331079 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000258168 | 1.083991656 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ST8SIA4 | 0.901071433 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, BCL2L1-AS1 | 1.262413164 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, NRSN2-AS1 | -1.275348201 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, STARD13-AS | 1.148054491 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, CFLAR-AS1 | 1.168941896 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, PRKAR1A | 1.257792414 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000226239 | 1.126077043 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, CTNNA3 | -1.819759686 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, KCNK5 | -2.491597199 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ESR2 | 1.071576206 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, SLC25A46 | 1.062235788 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, REV3L | 0.792446528 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ZC2HC1C | 2.027909336 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000279686 | -1.453758633 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ACER1 | -5.256214457 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, MALRD1 | -2.36001857 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, RRBP1 | -0.837125744 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ZNF451-AS1 | 1.853753635 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, SHANK2 | -1.481833304 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000248388 | 2.196067138 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, KPNA5 | 0.936135624 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, APPAT | -1.750949862 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, PCNT | -0.932423432 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000233848 | 2.752498803 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, MORF4L2 | 1.28059543 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000236283 | -1.572597604 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, SNRNP70 | -0.883484114 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, EXD3 | -0.805539835 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, CNTNAP5 | -2.392758482 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, CASR | -2.323412555 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ENSG00000285692 | 1.124516569 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, WDR81 | -2.102548546 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ZNF160 | -0.907890266 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, CA12 | -1.63720477 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, MAPK8IP3 | -0.998528168 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, ABTB3 | -2.945080572 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, CHORDC1 | 1.047593755 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, FREM1 | -1.948982139 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, FXYD6-AS1 | 2.22442108 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, SPACA6 | -1.045439073 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-1, AGBL1 | -2.851170905 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, NES | -2.451444521 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, ADARB2 | -3.212266234 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, SERPINB9 | 2.315559798 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, ENSG00000274422 | -2.329265154 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, BTNL9 | -2.01168798 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, CPEB2 | 1.51543417 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, TBX2 | -2.604511077 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, ENSG00000290560 | 2.378813977 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, CFAP54 | 1.988387042 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, ABI3BP | 1.57362138 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, SPACA6 | -1.724379529 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, ADAMTSL2 | -2.009897896 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, LZTS1 | -2.659531511 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, ENSG00000285744 | 1.889210245 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, ENSG00000225689 | -1.414674941 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, LUZP2 | -4.384000321 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, NCKAP5 | -1.592351284 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | EC-GC-2, FAT1 | -1.855192898 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | NKC-NKT, AGBL4 | -2.145446805 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | NKC-NKT, TFEC | 1.989578132 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | NKC-NKT, ENSG00000254186 | -2.913048038 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | NKC-NKT, PDE10A | -2.170777761 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | NKC-NKT, SHANK2 | -2.431773845 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | PEC, RGS6 | -3.331377896 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | PEC, AHNAK | -1.645129407 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | PT-2, LRRC4C | -2.167101922 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | PT-2, DSCAM | -3.104786855 log2 fold-change |
| Semaglutide 1.0 mg | Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy) | PT-2, RCN3 | -1.636040003 log2 fold-change |
Secondary
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.
Time frame: Baseline (week 0), End of treatment (week 52)
Population: Full analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall Number participants analyzed = number of participants with available data for particular timepoint, for the respective arms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 1.0 mg | Change in Glomerular Basement Membrane Width (Kidney Biopsy) | -72.67 Nanometer (nm) | Standard Deviation 96.6 |
| Placebo | Change in Glomerular Basement Membrane Width (Kidney Biopsy) | -8.66 Nanometer (nm) | Standard Deviation 206.35 |
Secondary
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.
Time frame: Baseline (week 0), End of treatment (week 52)
Population: Full analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall Number participants analyzed = number of participants with available data for particular timepoint, for the respective arms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 1.0 mg | Change in Kidney Function (Creatinine Clearance) (Urinalysis) | 3.8 Milliliter per minute | Standard Deviation 26.6 |
| Placebo | Change in Kidney Function (Creatinine Clearance) (Urinalysis) | -12.6 Milliliter per minute | Standard Deviation 34.2 |
Secondary
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.
Time frame: Baseline (week 0), End of treatment (week 52)
Population: Full analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall number of participants analyzed= FAS. Number Analyzed= number of participants with available data for particular timepoint, for the respective arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 1.0 mg | Change in Mean Arterial Flow (MRI) | Bilateral renalartery | 0.96 Ratio of mean arterial flow | Geometric Coefficient of Variation 24.96 |
| Semaglutide 1.0 mg | Change in Mean Arterial Flow (MRI) | Right renalartery | 0.97 Ratio of mean arterial flow | Geometric Coefficient of Variation 30.21 |
| Semaglutide 1.0 mg | Change in Mean Arterial Flow (MRI) | Left renalartery | 0.96 Ratio of mean arterial flow | Geometric Coefficient of Variation 25.06 |
| Placebo | Change in Mean Arterial Flow (MRI) | Bilateral renalartery | 0.96 Ratio of mean arterial flow | Geometric Coefficient of Variation 25.06 |
| Placebo | Change in Mean Arterial Flow (MRI) | Right renalartery | 0.95 Ratio of mean arterial flow | Geometric Coefficient of Variation 29.09 |
| Placebo | Change in Mean Arterial Flow (MRI) | Left renalartery | 0.98 Ratio of mean arterial flow | Geometric Coefficient of Variation 27.38 |
Secondary
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.
Time frame: Baseline (week 0), End of treatment (week 52)
Population: Full analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall number of participants analyzed= FAS. Number Analyzed= number of participants with available data for particular timepoint, for the respective arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 1.0 mg | Change in Mean Renal Artery Resistive Index (RARI) (MRI) | Bilateral renalartery | 0.97 Ratio of RARI | Geometric Coefficient of Variation 7 |
| Semaglutide 1.0 mg | Change in Mean Renal Artery Resistive Index (RARI) (MRI) | Right renalartery | 0.98 Ratio of RARI | Geometric Coefficient of Variation 8.38 |
| Semaglutide 1.0 mg | Change in Mean Renal Artery Resistive Index (RARI) (MRI) | Left renalartery | 0.97 Ratio of RARI | Geometric Coefficient of Variation 7.44 |
| Placebo | Change in Mean Renal Artery Resistive Index (RARI) (MRI) | Bilateral renalartery | 1.01 Ratio of RARI | Geometric Coefficient of Variation 6.13 |
| Placebo | Change in Mean Renal Artery Resistive Index (RARI) (MRI) | Right renalartery | 1.01 Ratio of RARI | Geometric Coefficient of Variation 8.62 |
| Placebo | Change in Mean Renal Artery Resistive Index (RARI) (MRI) | Left renalartery | 1.01 Ratio of RARI | Geometric Coefficient of Variation 6.43 |
Secondary
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.
Time frame: Baseline (week 0), End of treatment (week 52)
Population: Full analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall Number participants analyzed = number of participants with available data for particular timepoint, for the respective arms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 1.0 mg | Change in Natriuresis (Urinary Sodium Excretion) (Urinalysis) | -7.3 Millimoles per day (mmol/day) | Standard Deviation 71.3 |
| Placebo | Change in Natriuresis (Urinary Sodium Excretion) (Urinalysis) | -26.9 Millimoles per day (mmol/day) | Standard Deviation 85.2 |