Phase 3 N=9,651 Randomized Quadruple-blind Treatment

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

Diabetes Mellitus, Type 2

Bottom Line

View on ClinicalTrials.gov: NCT03914326 ↗

Enrolled (actual)

9,651

Serious AEs

49.1%

Results posted

Sep 2025

Primary outcome: Primary: 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 Participants — p=0.0028

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Semaglutide (Drug); Placebo (semaglutide) (Drug)
Age: Adult, Older Adult · 50+ yrs
Sex: All
Sponsor: Novo Nordisk A/S
Primary completion: Aug 2024

Outcome Measures

Outcome	Result	p-value
PRIMARY 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	0.0028 sig
SECONDARY 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	—
SECONDARY Number of Participants From Randomization to Time of Occurrence of CV Death	301; 320	—
SECONDARY 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	—
SECONDARY 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	—
SECONDARY 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	—
SECONDARY 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	—
SECONDARY 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	—
SECONDARY Number of Participants From Randomisation to Time to Occurrence of All-cause Death	528; 577	—
SECONDARY Number of Participants From Randomisation to First Occurrence of Non-fatal Myocardial Infarction (MI)	191; 253	—
SECONDARY Number of Participants From Randomisation to First Occurrence of Non-fatal Stroke	144; 161	—
SECONDARY Number of Participants From Randomisation to First Occurrence of Heart Failure Requiring Hospitalisation or Urgent Heart Failure Visit	146; 167	—
SECONDARY Number of Participants From Randomisation to First Occurrence of Coronary Revascularisation	200; 263	—
SECONDARY Number of Participants From Randomisation to First Occurrence of Unstable Angina Requiring Hospitalisation	74; 80	—
SECONDARY Number of Participants From Randomisation to Time to Occurrence of Renal Death	1; 7	—
SECONDARY Number of Participants From Randomisation to First Occurrence of Onset of Persistent 50% or More Reduction in eGFR	71; 86	—
SECONDARY 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	—
SECONDARY Number of Participants From Randomisation to First Occurrence of Initiation of Chronic Renal Replacement Therapy (Dialysis or Kidney Transplantation)	40; 48	—
SECONDARY Number of Participants From Randomisation to First Occurrence of Acute Limb Ischemia	16; 17	—
SECONDARY Number of Participants From Randomisation to First Occurrence of Chronic Limb Ischemia Hospitalisation	63; 88	—
SECONDARY Annual Rate of Change in eGFR (CKD-EPI) (Total eGFR Slope)	-1.67; -2.06	—
SECONDARY Change From Baseline in Glycosylated Haemoglobin (HbA1c)	-0.71; -0.15	—
SECONDARY Change From Baseline in Body Weight	-4.21; -1.28	—
SECONDARY Number of Severe Hypoglycaemic Episodes	88; 121	—
SECONDARY Number of Participants From Randomisation to First Occurrence of a Severe Hypoglycaemic Episode	76; 84	—

Summary

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.

Eligibility Criteria

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03914326). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.