A Phase 3 interventional study of Semaglutide and Placebo (semaglutide) in Diabetes Mellitus, Type 2, sponsored by Novo Nordisk A/S. Completed at 492 sites in 34 countries. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2025-12-11.
Sponsored by Novo Nordisk A/S · Phase 3, Interventional, and Treatment
The researchers are doing this study to look whether the type 2 diabetes medicine, semaglutide, has a positive effect on heart disease. Participants will either get semaglutide tablets or placebo tablets ("dummy" medicine) - which treatment is decided by chance. Participants must take one tablet with water every morning on an empty stomach and not eat or drink anything for at least 30 minutes. The study will last for about 3.5-5 years. Participants will have up to 25 clinic visits and 1 phone call with the study doctor. Women cannot be in the study if pregnant, breast-feeding or if they plan to become pregnant during the study period.
10,371 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,406 are open to participants now.
This study's enrollment of 9,651 is above the median of 80 across 8,350 interventional studies indexed under Diabetes Mellitus, Type 2.
Browse Diabetes Mellitus, Type 2 studies →Novo Nordisk A/S is the lead sponsor of 1,404 studies on the registry; 101 are open to participants now.
Of its 205 completed or terminated interventional studies of FDA-regulated products, 100 (49%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
At least one of the below conditions (a-d):
a) Coronary heart disease defined as at least one of the following: i. Prior myocardial infarction ii. Prior coronary revascularisation procedure iii. 50% or above stenosis in coronary artery documented by cardiac catheterisation, computerized tomography coronary angiography iv. Coronary heart disease with ischaemia documented by stress test with any imaging modality b) Cerebrovascular disease defined as at least one of the following: i. Prior stroke ii. Prior carotid artery revascularisation procedure iii.50% or above stenosis in carotid artery documented by X-ray angiography, magnetic resonance angiography, computerized tomography angiography or Doppler ultrasound c) Symptomatic peripheral artery disease (PAD) defined as at least one of the following: i. Intermittent claudication with an Ankle-brachial index (ABI) below 0.85 at rest ii. Intermittent claudication with a 50% or above stenosis in peripheral artery (excluding carotid) documented by X-ray angiography, magnetic resonance angiography, computerized tomography angiography or Doppler ultrasound iii. Prior peripheral artery (excluding carotid) revascularization procedure iv. Lower extremity amputation at or above ankle due to atherosclerotic disease (excluding e.g. trauma or osteomyelitis) d) Chronic kidney disease defined as: i. below 60 mL/min/1.73 m\^2 (based on medical records using latest available and no more than 6 months old assessment)
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
One tablet daily for 3.5 to 5 years
Drug: Semaglutide
One tablet daily for 3.5 to 5 years
Drug: Placebo (semaglutide)
Increasing doses (3 mg/7 mg/14 mg) of semaglutide tablets to be taken with water at the same time every morning in a fasting state
Placebo tablets to be taken with water at the same time every morning in a fasting state
Number of Participants From Randomization to First Occurrence of a Major Adverse Cardiovascular Event (MACE), a Composite Endpoint Consisting of: Cardiovascular (CV) Death/Non-fatal Myocardial Infarction/Non-fatal Stroke
Number of participants with first occurrence of EAC (event adjudication committee) confirmed major adverse cardiovascular event (MACE), a composite end-point. i.e., from time of randomization to first occurrence of cardiovascular (CV) death, non-fatal myocardial infarction and non-fatal stroke combined data 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: From randomisation (week 0) up to week 265
Number of Participants From Randomization to First Occurrence of CV Death;Renal Death;Onset of Persistent≥50% Reduction in eGFR(CKD-EPI);Onset of Persistent eGFR(CKD-EPI)<15 mL/Min/1.73m^2;Initiation of Chronic Renal Replacement Therapy
Number of participants with first occurrence of a composite endpoint. i.e., from time of randomization to first occurrence of CV death, renal death, onset of persistent greater than or equal to (≥) 50% reduction in estimated glomerular filtration rate (eGFR) (chronic kidney disease epidemiology collaboration CKD-EPI), onset of persistent eGFR (CKD-EPI) less than (\<)15 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2), initiation of chronic renal replacement therapy (dialysis or kidney transplantation) combined data 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: From randomisation (week 0) up to week 265
Number of Participants From Randomization to Time of Occurrence of CV Death
Number of participants from time of randomization to time to occurrence of EAC confirmed CV death 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: From randomisation (week 0) up to week 265
Number of Participants From Randomization to First Occurrence of Major Adverse Limb Events (MALE), a Composite Endpoint Consisting of: Acute Limb Ischemia Hospitalisation/Chronic Limb Ischemia Hospitalisation
Number of participants from randomization to first occurrence of EAC confirmed major adverse limb events (MALE), a composite endpoint consisting of: acute limb ischemia hospitalisation/chronic limb ischemia hospitalisation combined data 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: From randomisation (week 0) up to week 265
Number of Participants From Randomisation to First Occurrence of an Expanded MACE Composite Endpoint Consisting of: CV Death/Non-fatal Myocardial Infarction/ Non-fatal Stroke/Coronary Revascularisation/Unstable Angina Pectoris Requiring Hospitalisation
The number of participants from randomisation to first occurrence of an expanded MACE composite endpoint consisting of: CV death/non-fatal myocardial infarction/ non-fatal stroke/coronary revascularisation/unstable angina pectoris requiring hospitalisation combined data 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: From randomisation (week 0) up to week 265
Number of Participants From Randomisation to First Occurrence of a Composite Endpoint Consisting of : All-cause Death/ Non-fatal MI/ Non-fatal Stroke
The number of participants from randomisation to first occurrence of EAC confirmed composite endpoint consisting of : all-cause death/ non-fatal MI/ non-fatal stroke combined data 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: From randomisation (week 0) up to week 265
Number of Participants From Randomisation to First Occurrence of a Composite Heart Failure Endpoint Consisting of: CV Death/Heart Failure Requiring Hospitalisation/Urgent Heart Failure Visit
Number of participants from randomisation to first occurrence of EAC confirmed composite heart failure endpoint consisting of: CV death/heart failure requiring hospitalisation/urgent heart failure visit combined data 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: From randomisation (week 0) up to week 265
Number of Participants From Randomization to First Occurrence of CKD Endpoint:Renal Death;Onset of Persistent≥50% Reduction in eGFR (CKD-EPI);Onset of Persistent eGFR(CKD-EPI)<15 mL/Min/1.73 m^2;Initiation of Chronic Renal Replacement Therapy
The number of participants from randomization to first occurrence of CKD endpoint:renal death;onset of persistent≥50% reduction in eGFR (CKD-EPI);onset of persistent eGFR(CKD-EPI)\<15 mL/min/1.73 m\^2;initiation of chronic renal replacement therapy combined data 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: From randomisation (week 0) up to week 265
Number of Participants From Randomisation to Time to Occurrence of All-cause Death
The number of participants from randomisation to time to occurrence of EAC confirmed all-cause death 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: From randomisation (week 0) up to week 265
Number of Participants From Randomisation to First Occurrence of Non-fatal Myocardial Infarction (MI)
The number of participants from randomisation to first occurrence of EAC confirmed non-fatal MI 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: From randomisation (week 0) up to week 265
Number of Participants From Randomisation to First Occurrence of Non-fatal Stroke
The number of participants from randomisation to first occurrence of EAC confirmed non-fatal stroke 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: From randomisation (week 0) up to week 265
Number of Participants From Randomisation to First Occurrence of Heart Failure Requiring Hospitalisation or Urgent Heart Failure Visit
The number of participants from randomisation to first occurrence of EAC confirmed heart failure requiring hospitalisation or urgent heart failure visit 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: From randomisation (week 0) up to week 265
Number of Participants From Randomisation to First Occurrence of Coronary Revascularisation
The number of participants from randomisation to first occurrence of coronary revascularisation 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: From randomisation (week 0) up to week 265
Number of Participants From Randomisation to First Occurrence of Unstable Angina Requiring Hospitalisation
The number of participants from randomisation to first occurrence of EAC confirmed unstable angina requiring hospitalisation 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: From randomisation (week 0) up to week 265
Number of Participants From Randomisation to Time to Occurrence of Renal Death
The number of participants from randomisation to time to occurrence of EAC confirmed renal death 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: From randomisation (week 0) up to week 265
Number of Participants From Randomisation to First Occurrence of Onset of Persistent 50% or More Reduction in eGFR
The number of participants from randomisation to first occurrence of onset of persistent 50% or more reduction in eGFR during in-trial period were observed. 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 randomisation (week 0) up to week 265
Number of Participants From Randomisation to First Occurrence of Onset of Persistent eGFR (CKD-EPI) Below 15 mL/Min/1.73 m^2
The number of participants from randomisation to first occurrence of onset of persistent eGFR (CKD-EPI) below 15 mL/min/1.73 m\^2 during in-trial period were observed. 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 randomisation (week 0) up to week 265
Number of Participants From Randomisation to First Occurrence of Initiation of Chronic Renal Replacement Therapy (Dialysis or Kidney Transplantation)
The number of participants from randomisation to first occurrence of EAC confirmed initiation of chronic renal replacement therapy (dialysis or kidney transplantation) 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 randomisation (week 0) up to week 265
Number of Participants From Randomisation to First Occurrence of Acute Limb Ischemia
The number of participants from randomisation to first occurrence of EAC confirmed acute limb ischaemia hospitalization 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 randomisation (week 0) up to week 265
Number of Participants From Randomisation to First Occurrence of Chronic Limb Ischemia Hospitalisation
The number of participants from randomisation to first occurrence of EAC confirmed chronic limb ischaemia hospitalization 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 randomisation (week 0) up to week 265
Annual Rate of Change in eGFR (CKD-EPI) (Total eGFR Slope)
Annual rate of change in eGFR in terms of chronic kidney disease CKD-EPI were reported during 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 randomisation (week 0) up to week 260
Change From Baseline in Glycosylated Haemoglobin (HbA1c)
Change in HbA1c from baseline (Week 0) up 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
Change From Baseline in Body Weight
Change in body weight from baseline (Week 0) up 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
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 randomisation (week 0) up to week 265
Number of Participants From Randomisation to First Occurrence of a Severe Hypoglycaemic Episode
The number of participants from randomisation to first occurrence of severe hypoglycaemic episodes (such as the seriousness of hypoglycaemia, contributing factors, seizures, and unconsciousness; classified by American Diabetes Association) 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: From randomisation (week 0) up to week 265
The trial was conducted at 446 sites in 34 countries.
| Milestone | Oral Semaglutide | Placebo |
|---|---|---|
| Started | 4825 | 4826 |
| Full analysis set | 4825 | 4825 |
| Exposed | 4814 | 4816 |
| Completed | 4755 | 4740 |
| Not completed | 70 | 86 |
| Withdrew: Withdrawal by subject | 27 | 34 |
| Withdrew: Lost to follow-up | 43 | 51 |
| Withdrew: Randomised more than once | 0 | 1 |
Number of participants with first occurrence of EAC (event adjudication committee) confirmed major adverse cardiovascular event (MACE), a composite end-point. i.e., from time of randomization to first occurrence of cardiovascular (CV) death, non-fatal myocardial infarction and non-fatal stroke combined data 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomization to First Occurrence of a Major Adverse Cardiovascular Event (MACE), a Composite Endpoint Consisting of: Cardiovascular (CV) Death/Non-fatal Myocardial Infarction/Non-fatal Stroke | 579 | 668 |
Number of participants with first occurrence of a composite endpoint. i.e., from time of randomization to first occurrence of CV death, renal death, onset of persistent greater than or equal to (≥) 50% reduction in estimated glomerular filtration rate (eGFR) (chronic kidney disease epidemiology collaboration CKD-EPI), onset of persistent eGFR (CKD-EPI) less than (\<)15 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2), initiation of chronic renal replacement therapy (dialysis or kidney transplantation) combined data 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomization to First Occurrence of CV Death;Renal Death;Onset of Persistent≥50% Reduction in eGFR(CKD-EPI);Onset of Persistent eGFR(CKD-EPI)<15 mL/Min/1.73m^2;Initiation of Chronic Renal Replacement Therapy | 403 | 435 |
Number of participants from time of randomization to time to occurrence of EAC confirmed CV death 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomization to Time of Occurrence of CV Death | 301 | 320 |
Number of participants from randomization to first occurrence of EAC confirmed major adverse limb events (MALE), a composite endpoint consisting of: acute limb ischemia hospitalisation/chronic limb ischemia hospitalisation combined data 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomization to First Occurrence of Major Adverse Limb Events (MALE), a Composite Endpoint Consisting of: Acute Limb Ischemia Hospitalisation/Chronic Limb Ischemia Hospitalisation | 71 | 99 |
The number of participants from randomisation to first occurrence of an expanded MACE composite endpoint consisting of: CV death/non-fatal myocardial infarction/ non-fatal stroke/coronary revascularisation/unstable angina pectoris requiring hospitalisation combined data 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomisation to First Occurrence of an Expanded MACE Composite Endpoint Consisting of: CV Death/Non-fatal Myocardial Infarction/ Non-fatal Stroke/Coronary Revascularisation/Unstable Angina Pectoris Requiring Hospitalisation | 670 | 777 |
The number of participants from randomisation to first occurrence of EAC confirmed composite endpoint consisting of : all-cause death/ non-fatal MI/ non-fatal stroke combined data 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomisation to First Occurrence of a Composite Endpoint Consisting of : All-cause Death/ Non-fatal MI/ Non-fatal Stroke | 779 | 902 |
Number of participants from randomisation to first occurrence of EAC confirmed composite heart failure endpoint consisting of: CV death/heart failure requiring hospitalisation/urgent heart failure visit combined data 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
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomisation to First Occurrence of a Composite Heart Failure Endpoint Consisting of: CV Death/Heart Failure Requiring Hospitalisation/Urgent Heart Failure Visit | 405 | 443 |
The number of participants from randomization to first occurrence of CKD endpoint:renal death;onset of persistent≥50% reduction in eGFR (CKD-EPI);onset of persistent eGFR(CKD-EPI)\<15 mL/min/1.73 m\^2;initiation of chronic renal replacement therapy combined data 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomization to First Occurrence of CKD Endpoint:Renal Death;Onset of Persistent≥50% Reduction in eGFR (CKD-EPI);Onset of Persistent eGFR(CKD-EPI)<15 mL/Min/1.73 m^2;Initiation of Chronic Renal Replacement Therapy | 112 | 129 |
The number of participants from randomisation to time to occurrence of EAC confirmed all-cause death 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomisation to Time to Occurrence of All-cause Death | 528 | 577 |
The number of participants from randomisation to first occurrence of EAC confirmed non-fatal MI 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomisation to First Occurrence of Non-fatal Myocardial Infarction (MI) | 191 | 253 |
The number of participants from randomisation to first occurrence of EAC confirmed non-fatal stroke 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomisation to First Occurrence of Non-fatal Stroke | 144 | 161 |
The number of participants from randomisation to first occurrence of EAC confirmed heart failure requiring hospitalisation or urgent heart failure visit 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomisation to First Occurrence of Heart Failure Requiring Hospitalisation or Urgent Heart Failure Visit | 146 | 167 |
The number of participants from randomisation to first occurrence of coronary revascularisation 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomisation to First Occurrence of Coronary Revascularisation | 200 | 263 |
The number of participants from randomisation to first occurrence of EAC confirmed unstable angina requiring hospitalisation 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomisation to First Occurrence of Unstable Angina Requiring Hospitalisation | 74 | 80 |
The number of participants from randomisation to time to occurrence of EAC confirmed renal death 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomisation to Time to Occurrence of Renal Death | 1 | 7 |
The number of participants from randomisation to first occurrence of onset of persistent 50% or more reduction in eGFR during in-trial period were observed. 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomisation to First Occurrence of Onset of Persistent 50% or More Reduction in eGFR | 71 | 86 |
The number of participants from randomisation to first occurrence of onset of persistent eGFR (CKD-EPI) below 15 mL/min/1.73 m\^2 during in-trial period were observed. 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomisation to First Occurrence of Onset of Persistent eGFR (CKD-EPI) Below 15 mL/Min/1.73 m^2 | 23 | 33 |
The number of participants from randomisation to first occurrence of EAC confirmed initiation of chronic renal replacement therapy (dialysis or kidney transplantation) 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomisation to First Occurrence of Initiation of Chronic Renal Replacement Therapy (Dialysis or Kidney Transplantation) | 40 | 48 |
The number of participants from randomisation to first occurrence of EAC confirmed acute limb ischaemia hospitalization 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomisation to First Occurrence of Acute Limb Ischemia | 16 | 17 |
The number of participants from randomisation to first occurrence of EAC confirmed chronic limb ischaemia hospitalization 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomisation to First Occurrence of Chronic Limb Ischemia Hospitalisation | 63 | 88 |
Annual rate of change in eGFR in terms of chronic kidney disease CKD-EPI were reported during 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.
| ml/min/1.73 m^2 per year | Oral Semaglutide | Placebo |
|---|---|---|
| Annual Rate of Change in eGFR (CKD-EPI) (Total eGFR Slope) | -1.67 ± 0.0 | -2.06 ± 0.0 |
Change in HbA1c from baseline (Week 0) up 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.
| Percentage of HbA1c | Oral Semaglutide | Placebo |
|---|---|---|
| Change From Baseline in Glycosylated Haemoglobin (HbA1c) | -0.71 ± 1.22 | -0.15 ± 1.19 |
Change in body weight from baseline (Week 0) up 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.
| Kilograms | Oral Semaglutide | Placebo |
|---|---|---|
| Change From Baseline in Body Weight | -4.21 ± 5.85 | -1.28 ± 4.90 |
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.
| Episodes | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Severe Hypoglycaemic Episodes | 88 | 121 |
The number of participants from randomisation to first occurrence of severe hypoglycaemic episodes (such as the seriousness of hypoglycaemia, contributing factors, seizures, and unconsciousness; classified by American Diabetes Association) 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.
| Participants | Oral Semaglutide | Placebo |
|---|---|---|
| Number of Participants From Randomisation to First Occurrence of a Severe Hypoglycaemic Episode | 76 | 84 |
Collected over From Week 0 up to Week 265. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Oral Semaglutide | 528/4,825 (10.9%) | 2,312/4,825 (47.9%) | 1,761/4,825 (36.5%) |
| Placebo | 579/4,825 (12%) | 2,427/4,825 (50.3%) | 1,599/4,825 (33.1%) |
| Event | Oral Semaglutide | Placebo |
|---|---|---|
| Acute myocardial infarctionCardiac disorders | 175/4825 | 229/4825 |
| COVID-19 pneumoniaInfections and infestations | 138/4825 | 182/4825 |
| Acute kidney injuryRenal and urinary disorders | 123/4825 | 151/4825 |
| COVID-19Infections and infestations | 121/4825 | 141/4825 |
| PneumoniaInfections and infestations | 129/4825 | 129/4825 |
| Cardiac failureCardiac disorders | 107/4825 | 116/4825 |
| Coronary artery diseaseCardiac disorders | 102/4825 | 108/4825 |
| Angina unstableCardiac disorders | 80/4825 | 104/4825 |
| Angina pectorisCardiac disorders | 83/4825 | 103/4825 |
| Atrial fibrillationCardiac disorders | 99/4825 | 95/4825 |
| Event | Oral Semaglutide | Placebo |
|---|---|---|
| Diabetic retinopathyEye disorders | 943/4825 | 932/4825 |
| COVID-19Infections and infestations | 756/4825 | 777/4825 |
| NauseaGastrointestinal disorders | 344/4825 | 62/4825 |
Analysis of participants were performed on full analysis set (FAS) that was defined as all unique randomised participants and were grouped according to the treatment assigned at randomization.
| Age, Continuous(Years) | Oral Semaglutide | Placebo | Total |
|---|---|---|---|
| Mean | 66.1 ± 7.6 | 66.1 ± 7.5 | 66.1 ± 7.6 |
| Sex: Female, Male(Participants) | Oral Semaglutide | Placebo | Total |
|---|---|---|---|
| Female | 1376 | 1414 | 2790 |
| Male | 3449 | 3411 | 6860 |
| Ethnicity (NIH/OMB)(Participants) | Oral Semaglutide | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 674 | 706 | 1380 |
| Not Hispanic or Latino | 4106 | 4072 | 8178 |
| Unknown or Not Reported | 45 | 47 | 92 |
| Race (NIH/OMB)(Participants) | Oral Semaglutide | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 7 | 12 | 19 |
| Asian | 1134 | 1121 | 2255 |
| Native Hawaiian or Other Pacific Islander | 4 | 5 | 9 |
| Black or African American | 124 | 128 | 252 |
| White | 3327 | 3321 | 6648 |
| More than one race | 185 | 192 | 377 |
| Unknown or Not Reported | 44 | 46 | 90 |
Showing the first 100 of 492 sites across 34 countries. Choose a country and city above to see the rest.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Data sharing details ↗ · novonordisk-trials.com
Ran from Jun 2019 to primary completion in Aug 2024, 62 months.
Results were first posted in Sep 2025, 1 year after primary completion.
Of 438 industry-sponsored phase 3 interventional studies under Diabetes Mellitus, Type 2, half reached primary completion within 19 months of starting (the median), counting those still running; a quarter within 14 and three quarters within 26. This study's 62 months is above that.
Counting every sponsor, half of 525 studies reached it within 20 months; a quarter within 14 and three quarters within 30.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Nov 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Semaglutide