Diabetes Mellitus, Type 2
Conditions
Brief summary
The researchers are doing this study to see if semaglutide can slow down the growth and worsening of chronic kidney disease in people with type 2 diabetes. Participants will get semaglutide (active medicine) or placebo ('dummy medicine'). This is known as participants' study 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 in a skin fold once a week. The study will close when there is enough information collected to show clear result of the study. The total time participants will be in this study is about 3 to 5 years, but it could be longer.
Interventions
DRUGSemaglutide
Participants are to inject semaglutide with a needle in the stomach, thigh or upper arm. Participants will use a pen to inject semaglutide under their skin. Participants will inject semaglutide 1 time a week on the same day of the week. Participants' dose of semaglutide will be changed over time. Participants start by taking a smaller amount (0.25 mg). After 4 weeks the dose will be increased to 0.5 mg. It will be increased more (to 1 mg) at 8 weeks. Participants will then stay on the same dose for the rest of the study.
DRUGPlacebo (semaglutide)
Participants are to inject placebo (semaglutide) with a needle in the stomach, thigh or upper arm. Participants will use a pen to inject placebo (semaglutide) under their skin. Participants will inject placebo (semaglutide) 1 time a week on the same day of the week. Participants' dose of placebo (semaglutide) will be changed over time. Participants start by taking a smaller amount (0.25 mg). After 4 weeks the dose will be increased to 0.5 mg. It will be increased more (to 1 mg) at 8 weeks. Participants will then stay on the same dose for the rest of the study.
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. Japan: Male or female, age above or equal to 20 years at the time of signing informed consent * Diagnosed with type 2 diabetes mellitus * HbA1c less than or equal to 10% (less than or equal to 86 mmol/mol) * Renal impairment defined either by: 1. serum creatinine-based eGFR greater than or equal to 50 and less than or equal to 75 mL/min/1.73 m\^2 (CKD-EPI) and UACR greater than 300 and less than 5000 mg/g or 2. serum creatinine-based eGFR greater than or equal to 25 and less than 50 mL/min/1.73 m\^2 (CKD-EPI) and UACR greater than 100 and less than 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 an angiotensin II receptor blocker (ARB), unless such treatment is contraindicated or not tolerated. Treatment dose must be stable for at least 4 weeks prior to the date of the laboratory assessments used for determination of the inclusion criteria for renal impairment and kept stable until screening
Exclusion criteria
* Congenital or hereditary kidney diseases including polycystic kidney disease, autoimmune kidney diseases including glomerulonephritis or congenital urinary tract malformations * Use of any glucagon-like peptide-1 (GLP-1) receptor agonist within 30 days prior to screening * Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 60 days prior to the day of screening * Presently classified as being in New York Heart Association (NYHA) Class IV heart failure * Planned coronary, carotid or peripheral artery revascularisation * Current (or within 90 days) chronic or intermittent haemodialysis or peritoneal dialysis * 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 randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants From Time of Randomization to First Occurrence of Onset of Persistent ≥50% Reduction in eGFR(CKD-EPI); Onset of Persistent eGFR(CKD-EPI) <15mL/Min/1.73m^2; Initiation of Chronic Renal Replacement Therapy; Renal Death; CV Death | From Week 0 up to Week 234 | Number of participants with first composite renal event i.e., from time of randomization to first occurrence of an onset of persistent greater than or equal to (≥) 50 percent (%) reduction in estimated glomerular filtration rate (eGFR) (chronic kidney disease - epidemiology collaboration \[CKD-EPI\]), onset of persistent eGFR (CKD-EPI) \<15 milliliter per minute per 1.73 meter square (mL/min/1.73m\^2), initiation of chronic renal replacement therapy (dialysis or kidney transplantation), renal death, and cardiovascular (CV) death combined data were reported in this outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants From Time of Randomization to Occurrence of Onset of Persistent ≥50% Reduction in eGFR (CKD-EPI) | From Week 0 up to Week 234 | Number of participants from time of randomization to time to occurrence of onset of persistent ≥50% reduction in eGFR (CKD-EPI) were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Number of Participants From Time of Randomization to Occurrence of Onset of Persistent eGFR (CKD-EPI) <15mL/Min/1.73m^2 | From Week 0 up to Week 234 | Number of participants from time of randomization to time to occurrence of onset of persistent eGFR (CKD-EPI) \<15 mL/min/1.73m\^2 were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Number of Participants From Time of Randomization to Occurrence of Initiation of Chronic Renal Replacement Therapy | From Week 0 up to Week 234 | Number of participants from time of randomization to time to occurrence of initiation of chronic renal replacement therapy (dialysis or kidney transplantation) were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Number of Participants From Time of Randomization to Occurrence of Renal Death | From Week 0 up to Week 234 | Number of participants from time of randomization to time to occurrence of renal death were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Number of Participants From Time of Randomization to Occurrence of CV Death | From Week 0 up to Week 234 | Number of participants from time of randomization to time to occurrence of CV death were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Annual Rate of Change in eGFR (Chronic Kidney Disease CKD-EPI) (Chronic eGFR Slope) | Week 12, Week 234 | Annual rate of change in eGFR in terms of chronic kidney disease CKD-EPI were reported from Week 12 to Week 234 in-trial period. eGFR was calculated using the CKD-EPI formula. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Change From Baseline in eGFR (CKD-EPI) at Week 12 | Baseline (Week 0), Week 12 | Change from baseline in eGFR at Week 12 during in-trial period were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Change From Baseline in eGFR (Cystatin C CKD-EPI) at Week 104 | Baseline (Week 0), Week 104 | Changes from baseline in eGFR (cystatin C) at Week 104 in-trial period were reported. Cystatin C was calculated using the CKD-EPI formula. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Change From Baseline in Urinary Albumin-to-creatinine Ratio (UACR) at Week 104: Ratio to Baseline | Baseline (Week 0), Week 104 | Change from baseline in UACR (ratio to baseline) at Week 104 in-trial period were reported. For UACR, the baseline assessment is defined as the mean of the two assessments from the randomization visit. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Number of Participants From Time of Randomization to Time to First Occurrence of a Major Adverse Cardiovascular Event (MACE): Acute Myocardial Infarction (Non Fatal); Non-fatal Stroke; and CV Death | From Week 0 up to Week 234 | Number of participants who reported first occurence of non-fatal acute myocardial infarction, non-fatal stroke, and CV death combined data were presented from Week 0 up to Week 234 during on-treatment period. MACE consisted of non-fatal acute myocardial infarction, cardiovascular death and non-fatal stroke. First on-treatment period is defined as period from date of first dose until first time where no dose had been administered within 5 weeks (35 days) or end of the in-trial period, whichever came first. |
| Annual Rate of Change in eGFR (CKD-EPI) (Total eGFR Slope) | From Week 0 up to Week 234 | Annual rate of change in Total eGFR slope CKD-EPI were reported from baseline at Week 234 in-trial period. eGFR was calculated using the CKD-EPI formula. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Number of Participants From Time of Randomization to Time to Occurrence of Each of the Individual Components of the Confirmatory Secondary MACE Endpoint: Non-fatal Myocardial Infarction | From Week 0 up to Week 234 | Number of participants who reported occurrence of non-fatal acute myocardial infarction from Week 0 up to Week 234 during in-trial period were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Number of Participants From Time of Randomization to Time to Occurrence of Each of the Individual Components of the Confirmatory Secondary MACE Endpoint: Non-fatal Stroke | From Week 0 up to Week 234 | Number of participants who reported occurrence of non-fatal stroke from Week 0 up to Week 234 during in-trial period were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Number of Participants From Time of Randomization to Time to First Occurrence of Major Adverse Limb Events (MALE): Acute Limb Ischaemia Hospitalization and Chronic Limb Ischaemia Hospitalization | From Week 0 up to Week 234 | Number of participants with combined data of first occurence of acute limb ischaemia hospitalization and chronic limb ischaemia hospitalization from Week 0 up to Week 234 during on-treatment period were presented. MALE consisted of acute and chronic limb ischaemia hospitalisation. |
| Number of Participants With Acute Limb Ischaemia Hospitalization and Chronic Limb Ischaemia Hospitalization | From Week 0 up to Week 234 | Number of participants of acute limb ischaemia hospitalization and chronic limb ischaemia hospitalization from Week 0 up to Week 234 during in-trial period were presented. MALE consisted of acute and chronic limb ischaemia hospitalisation. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Change From Baseline in Body Weight at Week 104 | Baeline (Week 0), Week 104 | Change in body weight from Week 0 up to Week 104 during in-trial period, measured in kilograms, were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Change From Baseline in Glycosylated Haemoglobin (HbA1c) at Week 104 | Baseline (Week 0), Week 104 | Change in HbA1c from Week 0 to Week 104 during in-trial period, measured in percentage point of HbA1c, were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Change From Baseline in Systolic Blood Pressure at Week 104 | Baseline (Week 0), Week 104 | Change in systolic blood pressure from Week 0 to Week 104 during in-trial period were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Change From Baseline in Diastolic Blood Pressure at Week 104 | Baseline (Week 0), Week 104 | Change in diastolic blood pressure from Week 0 to Week 104 during in-trial period were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Number of Severe Hypoglycaemic Episodes | From Week 0 up to Week 234 | The number of severe hypoglycaemic episodes (such as the seriousness of hypoglycaemia, contributing factors, seizures, and unconsciousness; classified by American Diabetes Association) observed during the in-trial period were reported in this endpoint. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
| Number of Participants From Time of Randomization to Time to Occurrence of All-cause Death | From Week 0 up to Week 234 | Number of participants who reported occurence of deaths from Week 0 up to Week 234 during in-trial period were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Poland, Russia, Slovakia, South Africa, Spain, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Trial participants were randomized to treatment at 383 sites in 28 countries as follows: Argentina (7); Australia (7); Belgium (8); Brazil (7); Bulgaria (7); Canada (25); China (4); France (11); Germany (9); Greece (13); Hungary (10); India (16); Israel (4); Italy (8); Japan (26); Malaysia (6); Mexico (6); Netherlands (9); Poland (7); Russia (21); Slovakia (10); South Africa (8); Spain (7); Thailand (6); Turkey (12); Ukraine (7); United Kingdom (11); and United States (111).
Pre-assignment details
A total of 3533 eligible participants were randomized (1:1) to treatment with semaglutide 1 milligram (mg) (1767) or placebo (1766). The study included a treatment period (up to 60 months or more) and a follow-up period (5 weeks).
Participants by arm
| Arm | Count |
|---|---|
| Semaglutide Participants received a dose of semaglutide subcutaneously once weekly with dose escalation in every 4 weeks in doses 0.25 mg (weeks 0-3), 0.50 mg (weeks 4-7) until the maintenance dose of 1 mg was reached at week 8 and continued 1 mg dose along with standard of care until end of the study (week 238). Participants were followed up for 5 weeks after end of treatment. | 1,767 |
| Placebo Participants received placebo matching semaglutide subcutaneously once weekly along with standard of care until end of the study (week 238). Participants were followed up for 5 weeks after end of treatment. | 1,766 |
| Total | 3,533 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 23 | 30 |
| Overall Study | Withdrawal by Subject | 20 | 28 |
Baseline characteristics
| Characteristic | Placebo | Total | Semaglutide |
|---|---|---|---|
| Age, Continuous | 66.7 Years STANDARD_DEVIATION 9 | 66.6 Years STANDARD_DEVIATION 9 | 66.6 Years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 283 Participants | 556 Participants | 273 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1411 Participants | 2832 Participants | 1421 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 72 Participants | 145 Participants | 73 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 16 Participants | 25 Participants | 9 Participants |
| Race/Ethnicity, Customized Race Asian | 407 Participants | 846 Participants | 439 Participants |
| Race/Ethnicity, Customized Race Black or African American | 82 Participants | 160 Participants | 78 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 3 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Not reported | 40 Participants | 79 Participants | 39 Participants |
| Race/Ethnicity, Customized Race Other | 50 Participants | 95 Participants | 45 Participants |
| Race/Ethnicity, Customized Race White | 1168 Participants | 2323 Participants | 1155 Participants |
| Sex: Female, Male Female | 550 Participants | 1069 Participants | 519 Participants |
| Sex: Female, Male Male | 1216 Participants | 2464 Participants | 1248 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 227 / 1,767 | 279 / 1,766 |
| other Total, other adverse events | 507 / 1,767 | 522 / 1,766 |
| serious Total, serious adverse events | 877 / 1,767 | 950 / 1,766 |
Outcome results
Primary
Number of Participants From Time of Randomization to First Occurrence of Onset of Persistent ≥50% Reduction in eGFR(CKD-EPI); Onset of Persistent eGFR(CKD-EPI) <15mL/Min/1.73m^2; Initiation of Chronic Renal Replacement Therapy; Renal Death; CV Death
Number of participants with first composite renal event i.e., from time of randomization to first occurrence of an onset of persistent greater than or equal to (≥) 50 percent (%) reduction in estimated glomerular filtration rate (eGFR) (chronic kidney disease - epidemiology collaboration \[CKD-EPI\]), onset of persistent eGFR (CKD-EPI) \<15 milliliter per minute per 1.73 meter square (mL/min/1.73m\^2), initiation of chronic renal replacement therapy (dialysis or kidney transplantation), renal death, and cardiovascular (CV) death combined data were reported in this outcome measure.
Time frame: From Week 0 up to Week 234
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Semaglutide | Number of Participants From Time of Randomization to First Occurrence of Onset of Persistent ≥50% Reduction in eGFR(CKD-EPI); Onset of Persistent eGFR(CKD-EPI) <15mL/Min/1.73m^2; Initiation of Chronic Renal Replacement Therapy; Renal Death; CV Death | 331 Participants |
| Placebo | Number of Participants From Time of Randomization to First Occurrence of Onset of Persistent ≥50% Reduction in eGFR(CKD-EPI); Onset of Persistent eGFR(CKD-EPI) <15mL/Min/1.73m^2; Initiation of Chronic Renal Replacement Therapy; Renal Death; CV Death | 410 Participants |
Comparison: Time from randomization to first composite renal event was analyzed using a Cox proportional hazards model with treatment as categorical fixed factor and stratified by use of sodium glucose cotransporter-2 (SGLT-2) inhibitor (yes/no) at baseline. Based on the available number of events for analysis, the nominal significance level was updated to 0.01612 using the Lan-DeMets alpha spending function. eGFR was calculated using the CKD-EPI formula.p-value: 0.000195% CI: [0.66, 0.88]Regression, Cox
Secondary
Annual Rate of Change in eGFR (Chronic Kidney Disease CKD-EPI) (Chronic eGFR Slope)
Annual rate of change in eGFR in terms of chronic kidney disease CKD-EPI were reported from Week 12 to Week 234 in-trial period. eGFR was calculated using the CKD-EPI formula. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: Week 12, Week 234
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization. Here 'overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Annual Rate of Change in eGFR (Chronic Kidney Disease CKD-EPI) (Chronic eGFR Slope) | -2.36 mL/min/1.73 m^2 | Standard Error 0.1 |
| Placebo | Annual Rate of Change in eGFR (Chronic Kidney Disease CKD-EPI) (Chronic eGFR Slope) | -3.30 mL/min/1.73 m^2 | Standard Error 0.1 |
Secondary
Annual Rate of Change in eGFR (CKD-EPI) (Total eGFR Slope)
Annual rate of change in Total eGFR slope CKD-EPI were reported from baseline at Week 234 in-trial period. eGFR was calculated using the CKD-EPI formula. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: From Week 0 up to Week 234
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Annual Rate of Change in eGFR (CKD-EPI) (Total eGFR Slope) | -2.19 (mL/min/1.73 m^2)/year | Standard Error 0.1 |
| Placebo | Annual Rate of Change in eGFR (CKD-EPI) (Total eGFR Slope) | -3.36 (mL/min/1.73 m^2)/year | Standard Error 0.1 |
Secondary
Change From Baseline in Body Weight at Week 104
Change in body weight from Week 0 up to Week 104 during in-trial period, measured in kilograms, were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: Baeline (Week 0), Week 104
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization. Here 'overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change From Baseline in Body Weight at Week 104 | -5.54 Kilograms | Standard Deviation 6.57 |
| Placebo | Change From Baseline in Body Weight at Week 104 | -1.43 Kilograms | Standard Deviation 6.33 |
Secondary
Change From Baseline in Diastolic Blood Pressure at Week 104
Change in diastolic blood pressure from Week 0 to Week 104 during in-trial period were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: Baseline (Week 0), Week 104
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization. Here 'overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change From Baseline in Diastolic Blood Pressure at Week 104 | -0.4 millimeters of mercury | Standard Deviation 9.6 |
| Placebo | Change From Baseline in Diastolic Blood Pressure at Week 104 | -0.8 millimeters of mercury | Standard Deviation 10.4 |
Secondary
Change From Baseline in eGFR (CKD-EPI) at Week 12
Change from baseline in eGFR at Week 12 during in-trial period were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: Baseline (Week 0), Week 12
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization. Here 'overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change From Baseline in eGFR (CKD-EPI) at Week 12 | -1.07 mL/min/1.73m^2 | Standard Deviation 8.16 |
| Placebo | Change From Baseline in eGFR (CKD-EPI) at Week 12 | -1.07 mL/min/1.73m^2 | Standard Deviation 7.73 |
Secondary
Change From Baseline in eGFR (Cystatin C CKD-EPI) at Week 104
Changes from baseline in eGFR (cystatin C) at Week 104 in-trial period were reported. Cystatin C was calculated using the CKD-EPI formula. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: Baseline (Week 0), Week 104
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization. Here 'overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change From Baseline in eGFR (Cystatin C CKD-EPI) at Week 104 | -2.1 mL/min/1.73m^2 | Standard Deviation 11.4 |
| Placebo | Change From Baseline in eGFR (Cystatin C CKD-EPI) at Week 104 | -5.4 mL/min/1.73m^2 | Standard Deviation 9.7 |
Secondary
Change From Baseline in Glycosylated Haemoglobin (HbA1c) at Week 104
Change in HbA1c from Week 0 to Week 104 during in-trial period, measured in percentage point of HbA1c, were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: Baseline (Week 0), Week 104
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization. Here 'overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change From Baseline in Glycosylated Haemoglobin (HbA1c) at Week 104 | -0.86 Percentage of HbA1c | Standard Deviation 1.35 |
| Placebo | Change From Baseline in Glycosylated Haemoglobin (HbA1c) at Week 104 | -0.04 Percentage of HbA1c | Standard Deviation 1.29 |
Secondary
Change From Baseline in Systolic Blood Pressure at Week 104
Change in systolic blood pressure from Week 0 to Week 104 during in-trial period were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: Baseline (Week 0), Week 104
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization. Here 'overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change From Baseline in Systolic Blood Pressure at Week 104 | -3.9 Millimeters of mercury | Standard Deviation 17.6 |
| Placebo | Change From Baseline in Systolic Blood Pressure at Week 104 | -1.4 Millimeters of mercury | Standard Deviation 18.3 |
Secondary
Change From Baseline in Urinary Albumin-to-creatinine Ratio (UACR) at Week 104: Ratio to Baseline
Change from baseline in UACR (ratio to baseline) at Week 104 in-trial period were reported. For UACR, the baseline assessment is defined as the mean of the two assessments from the randomization visit. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: Baseline (Week 0), Week 104
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization. Here 'overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change From Baseline in Urinary Albumin-to-creatinine Ratio (UACR) at Week 104: Ratio to Baseline | 0.60 Ratio | Geometric Coefficient of Variation 224.09 |
| Placebo | Change From Baseline in Urinary Albumin-to-creatinine Ratio (UACR) at Week 104: Ratio to Baseline | 0.89 Ratio | Geometric Coefficient of Variation 211.7 |
Secondary
Number of Participants From Time of Randomization to Occurrence of CV Death
Number of participants from time of randomization to time to occurrence of CV death were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: From Week 0 up to Week 234
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Semaglutide | Number of Participants From Time of Randomization to Occurrence of CV Death | 123 Participants |
| Placebo | Number of Participants From Time of Randomization to Occurrence of CV Death | 169 Participants |
Secondary
Number of Participants From Time of Randomization to Occurrence of Initiation of Chronic Renal Replacement Therapy
Number of participants from time of randomization to time to occurrence of initiation of chronic renal replacement therapy (dialysis or kidney transplantation) were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: From Week 0 up to Week 234
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Semaglutide | Number of Participants From Time of Randomization to Occurrence of Initiation of Chronic Renal Replacement Therapy | 87 Participants |
| Placebo | Number of Participants From Time of Randomization to Occurrence of Initiation of Chronic Renal Replacement Therapy | 100 Participants |
Secondary
Number of Participants From Time of Randomization to Occurrence of Onset of Persistent ≥50% Reduction in eGFR (CKD-EPI)
Number of participants from time of randomization to time to occurrence of onset of persistent ≥50% reduction in eGFR (CKD-EPI) were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: From Week 0 up to Week 234
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Semaglutide | Number of Participants From Time of Randomization to Occurrence of Onset of Persistent ≥50% Reduction in eGFR (CKD-EPI) | 165 Participants |
| Placebo | Number of Participants From Time of Randomization to Occurrence of Onset of Persistent ≥50% Reduction in eGFR (CKD-EPI) | 213 Participants |
Secondary
Number of Participants From Time of Randomization to Occurrence of Onset of Persistent eGFR (CKD-EPI) <15mL/Min/1.73m^2
Number of participants from time of randomization to time to occurrence of onset of persistent eGFR (CKD-EPI) \<15 mL/min/1.73m\^2 were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: From Week 0 up to Week 234
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Semaglutide | Number of Participants From Time of Randomization to Occurrence of Onset of Persistent eGFR (CKD-EPI) <15mL/Min/1.73m^2 | 92 Participants |
| Placebo | Number of Participants From Time of Randomization to Occurrence of Onset of Persistent eGFR (CKD-EPI) <15mL/Min/1.73m^2 | 110 Participants |
Secondary
Number of Participants From Time of Randomization to Occurrence of Renal Death
Number of participants from time of randomization to time to occurrence of renal death were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: From Week 0 up to Week 234
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Semaglutide | Number of Participants From Time of Randomization to Occurrence of Renal Death | 5 Participants |
| Placebo | Number of Participants From Time of Randomization to Occurrence of Renal Death | 5 Participants |
Secondary
Number of Participants From Time of Randomization to Time to First Occurrence of a Major Adverse Cardiovascular Event (MACE): Acute Myocardial Infarction (Non Fatal); Non-fatal Stroke; and CV Death
Number of participants who reported first occurence of non-fatal acute myocardial infarction, non-fatal stroke, and CV death combined data were presented from Week 0 up to Week 234 during on-treatment period. MACE consisted of non-fatal acute myocardial infarction, cardiovascular death and non-fatal stroke. First on-treatment period is defined as period from date of first dose until first time where no dose had been administered within 5 weeks (35 days) or end of the in-trial period, whichever came first.
Time frame: From Week 0 up to Week 234
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Semaglutide | Number of Participants From Time of Randomization to Time to First Occurrence of a Major Adverse Cardiovascular Event (MACE): Acute Myocardial Infarction (Non Fatal); Non-fatal Stroke; and CV Death | 212 Participants |
| Placebo | Number of Participants From Time of Randomization to Time to First Occurrence of a Major Adverse Cardiovascular Event (MACE): Acute Myocardial Infarction (Non Fatal); Non-fatal Stroke; and CV Death | 254 Participants |
Secondary
Number of Participants From Time of Randomization to Time to First Occurrence of Major Adverse Limb Events (MALE): Acute Limb Ischaemia Hospitalization and Chronic Limb Ischaemia Hospitalization
Number of participants with combined data of first occurence of acute limb ischaemia hospitalization and chronic limb ischaemia hospitalization from Week 0 up to Week 234 during on-treatment period were presented. MALE consisted of acute and chronic limb ischaemia hospitalisation.
Time frame: From Week 0 up to Week 234
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Semaglutide | Number of Participants From Time of Randomization to Time to First Occurrence of Major Adverse Limb Events (MALE): Acute Limb Ischaemia Hospitalization and Chronic Limb Ischaemia Hospitalization | 16 Participants |
| Placebo | Number of Participants From Time of Randomization to Time to First Occurrence of Major Adverse Limb Events (MALE): Acute Limb Ischaemia Hospitalization and Chronic Limb Ischaemia Hospitalization | 28 Participants |
Secondary
Number of Participants From Time of Randomization to Time to Occurrence of All-cause Death
Number of participants who reported occurence of deaths from Week 0 up to Week 234 during in-trial period were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: From Week 0 up to Week 234
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Semaglutide | Number of Participants From Time of Randomization to Time to Occurrence of All-cause Death | 227 Participants |
| Placebo | Number of Participants From Time of Randomization to Time to Occurrence of All-cause Death | 279 Participants |
Secondary
Number of Participants From Time of Randomization to Time to Occurrence of Each of the Individual Components of the Confirmatory Secondary MACE Endpoint: Non-fatal Myocardial Infarction
Number of participants who reported occurrence of non-fatal acute myocardial infarction from Week 0 up to Week 234 during in-trial period were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: From Week 0 up to Week 234
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Semaglutide | Number of Participants From Time of Randomization to Time to Occurrence of Each of the Individual Components of the Confirmatory Secondary MACE Endpoint: Non-fatal Myocardial Infarction | 52 Participants |
| Placebo | Number of Participants From Time of Randomization to Time to Occurrence of Each of the Individual Components of the Confirmatory Secondary MACE Endpoint: Non-fatal Myocardial Infarction | 64 Participants |
Secondary
Number of Participants From Time of Randomization to Time to Occurrence of Each of the Individual Components of the Confirmatory Secondary MACE Endpoint: Non-fatal Stroke
Number of participants who reported occurrence of non-fatal stroke from Week 0 up to Week 234 during in-trial period were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: From Week 0 up to Week 234
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Semaglutide | Number of Participants From Time of Randomization to Time to Occurrence of Each of the Individual Components of the Confirmatory Secondary MACE Endpoint: Non-fatal Stroke | 63 Participants |
| Placebo | Number of Participants From Time of Randomization to Time to Occurrence of Each of the Individual Components of the Confirmatory Secondary MACE Endpoint: Non-fatal Stroke | 51 Participants |
Secondary
Number of Participants With Acute Limb Ischaemia Hospitalization and Chronic Limb Ischaemia Hospitalization
Number of participants of acute limb ischaemia hospitalization and chronic limb ischaemia hospitalization from Week 0 up to Week 234 during in-trial period were presented. MALE consisted of acute and chronic limb ischaemia hospitalisation. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: From Week 0 up to Week 234
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide | Number of Participants With Acute Limb Ischaemia Hospitalization and Chronic Limb Ischaemia Hospitalization | Acute limb ischaemia hospitalization | 1 Participants |
| Semaglutide | Number of Participants With Acute Limb Ischaemia Hospitalization and Chronic Limb Ischaemia Hospitalization | Chronic limb ischaemia hospitalization | 16 Participants |
| Placebo | Number of Participants With Acute Limb Ischaemia Hospitalization and Chronic Limb Ischaemia Hospitalization | Acute limb ischaemia hospitalization | 3 Participants |
| Placebo | Number of Participants With Acute Limb Ischaemia Hospitalization and Chronic Limb Ischaemia Hospitalization | Chronic limb ischaemia hospitalization | 25 Participants |
Secondary
Number of Severe Hypoglycaemic Episodes
The number of severe hypoglycaemic episodes (such as the seriousness of hypoglycaemia, contributing factors, seizures, and unconsciousness; classified by American Diabetes Association) observed during the in-trial period were reported in this endpoint. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.
Time frame: From Week 0 up to Week 234
Population: FAS included all unique randomized participants who were grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide | Number of Severe Hypoglycaemic Episodes | 37 Episodes |
| Placebo | Number of Severe Hypoglycaemic Episodes | 37 Episodes |