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CompletedPhase 3Results posted

A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes

Semaglutide Cardiovascular Outcomes Trial in Patients With Type 2 Diabetes

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Oral · GLP-1 agonist

Listed sites

492

Recruiting sites

-

Actual enrollment

9,651

Study population

Cardiovascular disease, Chronic kidney disease, Type 2 diabetes

Eligibility highlights

•HbA1c 6.5-10%•eGFR ≤60

Primary endpoint

•3-point MACE (Cardiovascular death, Non-fatal MI, Non-fatal stroke)

Registered trial locations

Locations reported to ClinicalTrials.gov for this trial snapshot. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT03914326
Org study IDEX9924-4473
Secondary ID2018-003141-42European Medicines Agency (EudraCT)
Secondary IDU1111-1218-5368World Health Organization (WHO)

Timeline

Milestones

Study first posted2019-04-16actual
Study start2019-06-17actual
Primary completion2024-08-23actual
Study completion2024-08-23actual
Results first posted2025-09-22actual
Last update posted2025-12-11actual

Assets

Investigational agents

Semaglutide

Who this study enrolls

Cardiovascular diseaseChronic kidney diseaseType 2 diabetes

Who can enroll

Minimum age50 Years
SexAll
Healthy volunteersNot accepted

Inclusion criteria

•Male or female, age equal to or above 50 years at the time of signing informed consent
•Diagnosed with type 2 diabetes mellitus
•HbA1c 6.5% - 10.0% (47 - 86 mmol/mol) (both inclusive) (latest available and no more than 30 days old local laboratory assessment based on medical records or point of care measurement)
•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. eGFR 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

•Any of the following: myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within the past 60 days prior to the day of screening
•Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
•Heart failure presently classified as being in New York Heart Association Class IV
•Treatment with any glucagon-like peptide-1 receptor agonist within 30 days before screening

Endpoints (50)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Cardiovascular outcomes
24
Renal / kidney
14
Heart failure
4
Safety / tolerability / PK
4
Weight & body composition
2
Glycemic / diabetes
2

Cardiovascular outcomes

24 endpoints
Primary/registry result

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

Time frame:From randomisation (week 0) up to week 265

3-point MACE

time to event, event

componentsCardiovascular death, Non-fatal MI, Non-fatal stroke

Posted result

GroupParticipants95% CI
Oral Semaglutide579-
Placebo668-
Hazard ratio (hr)0.8695% CI0.77 - 0.96p0.0028Regression, Cox
Primary/protocol endpoint

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

Time frame:From randomisation (week 0) up to week 265

3-point MACE

time to event, event

componentsCardiovascular death, Non-fatal MI, Non-fatal stroke

Secondary/registry result

Number of Participants From Randomization to Time of Occurrence of CV Death

Time frame:From randomisation (week 0) up to week 265

Cardiovascular death

time to event, event

Posted result

GroupParticipants95% CI
Oral Semaglutide301-
Placebo320-
Secondary/registry result

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

Time frame:From randomisation (week 0) up to week 265

MALE composite (major adverse limb events)

time to event, event

componentsAcute limb ischemia

Posted result

GroupParticipants95% CI
Oral Semaglutide71-
Placebo99-
Secondary/registry result

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

Time frame:From randomisation (week 0) up to week 265

5-point MACE

time to event, event

componentsCardiovascular death, Non-fatal MI, Non-fatal stroke, Coronary revascularization, Unstable angina hospitalization

Posted result

GroupParticipants95% CI
Oral Semaglutide670-
Placebo777-
Secondary/registry result

Number of Participants From Randomisation to First Occurrence of a Composite Endpoint Consisting of : All-cause Death/ Non-fatal MI/ Non-fatal Stroke

Time frame:From randomisation (week 0) up to week 265

Expanded / custom MACE composite

time to event, event

componentsAll-cause death, Non-fatal MI, Non-fatal stroke

Posted result

GroupParticipants95% CI
Oral Semaglutide779-
Placebo902-
Secondary/registry result

Number of Participants From Randomisation to Time to Occurrence of All-cause Death

Time frame:From randomisation (week 0) up to week 265

All-cause death

time to event, event

SNOMED 419620001

Posted result

GroupParticipants95% CI
Oral Semaglutide528-
Placebo577-
Secondary/registry result

Number of Participants From Randomisation to First Occurrence of Non-fatal Myocardial Infarction (MI)

Time frame:From randomisation (week 0) up to week 265

Non-fatal MI

time to event, event

SNOMED 22298006

Posted result

GroupParticipants95% CI
Oral Semaglutide191-
Placebo253-
Secondary/registry result

Number of Participants From Randomisation to First Occurrence of Non-fatal Stroke

Time frame:From randomisation (week 0) up to week 265

Non-fatal stroke

time to event, event

SNOMED 230690007

Posted result

GroupParticipants95% CI
Oral Semaglutide144-
Placebo161-
Secondary/registry result

Number of Participants From Randomisation to First Occurrence of Coronary Revascularisation

Time frame:From randomisation (week 0) up to week 265

Coronary revascularization

time to event, event

SNOMED 415070008

Posted result

GroupParticipants95% CI
Oral Semaglutide200-
Placebo263-
Secondary/registry result

Number of Participants From Randomisation to First Occurrence of Unstable Angina Requiring Hospitalisation

Time frame:From randomisation (week 0) up to week 265

Unstable angina hospitalization

time to event, event

Posted result

GroupParticipants95% CI
Oral Semaglutide74-
Placebo80-
Secondary/registry result

Number of Participants From Randomisation to First Occurrence of Acute Limb Ischemia

Time frame:From randomisation (week 0) up to week 265

Acute limb ischemia

time to event, event

Posted result

GroupParticipants95% CI
Oral Semaglutide16-
Placebo17-
Secondary/registry result

Number of Participants From Randomisation to First Occurrence of Chronic Limb Ischemia Hospitalisation

Time frame:From randomisation (week 0) up to week 265

Peripheral-artery outcome composite

time to event, event

Posted result

GroupParticipants95% CI
Oral Semaglutide63-
Placebo88-
Secondary/protocol endpoint

Number of Participants From Randomization to Time of Occurrence of CV Death

Time frame:From randomisation (week 0) up to week 265

Cardiovascular death

time to event, event

Secondary/protocol endpoint

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

Time frame:From randomisation (week 0) up to week 265

MALE composite (major adverse limb events)

time to event, event

componentsAcute limb ischemia, Peripheral-artery outcome composite

Secondary/protocol endpoint

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

Time frame:From randomisation (week 0) up to week 265

5-point MACE

time to event, event

componentsCardiovascular death, Non-fatal MI, Non-fatal stroke, Coronary revascularization, Unstable angina hospitalization

Secondary/protocol endpoint

Number of Participants From Randomisation to First Occurrence of a Composite Endpoint Consisting of : All-cause Death/ Non-fatal MI/ Non-fatal Stroke

Time frame:From randomisation (week 0) up to week 265

Expanded / custom MACE composite

time to event, event

componentsAll-cause death, Non-fatal MI, Non-fatal stroke

Secondary/protocol endpoint

Number of Participants From Randomisation to Time to Occurrence of All-cause Death

Time frame:From randomisation (week 0) up to week 265

All-cause death

time to event, event

SNOMED 419620001

Secondary/protocol endpoint

Number of Participants From Randomisation to First Occurrence of Non-fatal Myocardial Infarction (MI)

Time frame:From randomisation (week 0) up to week 265

Non-fatal MI

time to event, event

SNOMED 22298006

Secondary/protocol endpoint

Number of Participants From Randomisation to First Occurrence of Non-fatal Stroke

Time frame:From randomisation (week 0) up to week 265

Non-fatal stroke

time to event, event

SNOMED 230690007

Secondary/protocol endpoint

Number of Participants From Randomisation to First Occurrence of Coronary Revascularisation

Time frame:From randomisation (week 0) up to week 265

Coronary revascularization

time to event, event

SNOMED 415070008

Secondary/protocol endpoint

Number of Participants From Randomisation to First Occurrence of Unstable Angina Requiring Hospitalisation

Time frame:From randomisation (week 0) up to week 265

Unstable angina hospitalization

time to event, event

Secondary/protocol endpoint

Number of Participants From Randomisation to First Occurrence of Acute Limb Ischemia

Time frame:From randomisation (week 0) up to week 265

Acute limb ischemia

time to event, event

Secondary/protocol endpoint

Number of Participants From Randomisation to First Occurrence of Chronic Limb Ischemia Hospitalisation

Time frame:From randomisation (week 0) up to week 265

time to event, event

Weight & body composition

2 endpoints
Secondary/registry result

Change From Baseline in Body Weight

Time frame:Baseline (Week 0), Week 104

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

GroupMean · Kilograms95% CI
Oral Semaglutide-4.21-
Placebo-1.28-
Secondary/protocol endpoint

Change From Baseline in Body Weight

Time frame:Baseline (Week 0), Week 104

Body weight, absolute change (kg)

change from baseline, improvement

Glycemic / diabetes

2 endpoints
Secondary/registry result

Change From Baseline in Glycosylated Haemoglobin (HbA1c)

Time frame:Baseline (Week 0), Week 104

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

GroupMean · % HbA1c95% CI
Oral Semaglutide-0.71-
Placebo-0.15-
Secondary/protocol endpoint

Change From Baseline in Glycosylated Haemoglobin (HbA1c)

Time frame:Baseline (Week 0), Week 104

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Heart failure

4 endpoints
Secondary/registry result

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

Time frame:From randomisation (week 0) up to week 265

Heart-failure composite

time to event, event

componentsCardiovascular death, Heart-failure hospitalization, Urgent heart-failure visit

Posted result

GroupParticipants95% CI
Oral Semaglutide405-
Placebo443-
Secondary/registry result

Number of Participants From Randomisation to First Occurrence of Heart Failure Requiring Hospitalisation or Urgent Heart Failure Visit

Time frame:From randomisation (week 0) up to week 265

Heart-failure composite

time to event, event

componentsHeart-failure hospitalization, Urgent heart-failure visit

SNOMED 84114007

Posted result

GroupParticipants95% CI
Oral Semaglutide146-
Placebo167-
Secondary/protocol endpoint

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

Time frame:From randomisation (week 0) up to week 265

Heart-failure composite

time to event, event

componentsCardiovascular death, Heart-failure hospitalization, Urgent heart-failure visit

Secondary/protocol endpoint

Number of Participants From Randomisation to First Occurrence of Heart Failure Requiring Hospitalisation or Urgent Heart Failure Visit

Time frame:From randomisation (week 0) up to week 265

Heart-failure composite

time to event, event

componentsHeart-failure hospitalization, Urgent heart-failure visit

SNOMED 84114007

Renal / kidney

14 endpoints
Secondary/registry result

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

Time frame:From randomisation (week 0) up to week 265

Custom renal composite

time to event, event

componentsCardiovascular death, Renal death, eGFR, change, End-stage renal disease, Kidney-replacement therapy

Posted result

GroupParticipants95% CI
Oral Semaglutide403-
Placebo435-
Secondary/registry result

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

Time frame:From randomisation (week 0) up to week 265

Custom renal composite

composite event, event

componentsRenal death, eGFR, change, End-stage renal disease, Kidney-replacement therapy

Posted result

GroupParticipants95% CI
Oral Semaglutide112-
Placebo129-
Secondary/registry result

Number of Participants From Randomisation to Time to Occurrence of Renal Death

Time frame:From randomisation (week 0) up to week 265

Renal death

time to event, event

Posted result

GroupParticipants95% CI
Oral Semaglutide1-
Placebo7-
Secondary/registry result

Number of Participants From Randomisation to First Occurrence of Onset of Persistent 50% or More Reduction in eGFR

Time frame:From randomisation (week 0) up to week 265

Custom renal composite

time to event, event

LOINC 98979-8

Posted result

GroupParticipants95% CI
Oral Semaglutide71-
Placebo86-
Secondary/registry result

Number of Participants From Randomisation to First Occurrence of Onset of Persistent eGFR (CKD-EPI) Below 15 mL/Min/1.73 m^2

Time frame:From randomisation (week 0) up to week 265

End-stage renal disease

time to event, event

Posted result

GroupParticipants95% CI
Oral Semaglutide23-
Placebo33-
Secondary/registry result

Number of Participants From Randomisation to First Occurrence of Initiation of Chronic Renal Replacement Therapy (Dialysis or Kidney Transplantation)

Time frame:From randomisation (week 0) up to week 265

Kidney-replacement therapy

time to event, event

componentsKidney-replacement therapy

Posted result

GroupParticipants95% CI
Oral Semaglutide40-
Placebo48-
Secondary/registry result

Annual Rate of Change in eGFR (CKD-EPI) (Total eGFR Slope)

Time frame:From randomisation (week 0) up to week 260

eGFR slope (total)

change from baseline, improvement

LOINC 98979-8

Posted result

GroupMean · ml/min/1.73 m^2 per year95% CI
Oral Semaglutide-1.67-
Placebo-2.06-
Secondary/protocol endpoint

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

Time frame:From randomisation (week 0) up to week 265

Custom renal composite

time to event, event

componentsCardiovascular death, Renal death, eGFR, change, End-stage renal disease, Kidney-replacement therapy

Secondary/protocol endpoint

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

Time frame:From randomisation (week 0) up to week 265

Custom renal composite

time to event, event

componentsRenal death, eGFR, change, End-stage renal disease, Kidney-replacement therapy

Secondary/protocol endpoint

Number of Participants From Randomisation to Time to Occurrence of Renal Death

Time frame:From randomisation (week 0) up to week 265

Renal death

time to event, event

Secondary/protocol endpoint

Number of Participants From Randomisation to First Occurrence of Onset of Persistent 50% or More Reduction in eGFR

Time frame:From randomisation (week 0) up to week 265

Custom renal composite

time to event, event

LOINC 98979-8

Secondary/protocol endpoint

Number of Participants From Randomisation to First Occurrence of Onset of Persistent eGFR (CKD-EPI) Below 15 mL/Min/1.73 m^2

Time frame:From randomisation (week 0) up to week 265

End-stage renal disease

time to event, event

LOINC 98979-8 SNOMED 46177005

Secondary/protocol endpoint

Number of Participants From Randomisation to First Occurrence of Initiation of Chronic Renal Replacement Therapy (Dialysis or Kidney Transplantation)

Time frame:From randomisation (week 0) up to week 265

Kidney-replacement therapy

time to event, event

componentsKidney-replacement therapy

Secondary/protocol endpoint

Annual Rate of Change in eGFR (CKD-EPI) (Total eGFR Slope)

Time frame:From randomisation (week 0) up to week 260

eGFR slope (total)

change from baseline, improvement

LOINC 98979-8

Safety / tolerability / PK

4 endpoints
Secondary/registry result

Number of Severe Hypoglycaemic Episodes

Time frame:From randomisation (week 0) up to week 265

Severe hypoglycemia

event count, event

Posted result

GroupNumber · Episodes95% CI
Oral Semaglutide88-
Placebo121-
Secondary/registry result

Number of Participants From Randomisation to First Occurrence of a Severe Hypoglycaemic Episode

Time frame:From randomisation (week 0) up to week 265

Severe hypoglycemia

time to event, event

Posted result

GroupParticipants95% CI
Oral Semaglutide76-
Placebo84-
Secondary/protocol endpoint

Number of Severe Hypoglycaemic Episodes

Time frame:From randomisation (week 0) up to week 265

Severe hypoglycemia

event count, event

Secondary/protocol endpoint

Number of Participants From Randomisation to First Occurrence of a Severe Hypoglycaemic Episode

Time frame:From randomisation (week 0) up to week 265

Severe hypoglycemia

time to event, event

Publications (11)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 6, 2026
Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)
Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 6, 2026 snapshot.