Phase 3
N=17,604
Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity
Overweight · Obesity
Bottom Line
View on ClinicalTrials.gov: NCT03574597 ↗Enrolled (actual)
17,604
Serious AEs
34.9%
Results posted
Aug 2024
Primary outcome: Primary: Participants From Time of Randomization to First Occurrence of a Composite Outcome Measure Consisting of: Cardiovascular (CV) Death, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke — 569; 701 Participants — p=< 0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Semaglutide (Drug); Placebo (semaglutide) (Drug)
- Age
- Adult, Older Adult · 45+ yrs
- Sex
- All
- Sponsor
- Novo Nordisk A/S
- Primary completion
- Jun 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Participants From Time of Randomization to First Occurrence of a Composite Outcome Measure Consisting of: Cardiovascular (CV) Death, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke |
569; 701 | < 0.0001 sig |
| SECONDARY Participants From Time of Randomisation to CV Death |
223; 262 | — |
| SECONDARY Participants From Time of Randomisation to First Occurrence of a Composite Heart Failure (HF) Outcome Measure Consisting of: HF Hospitalisation, Urgent HF Visit or CV Death |
300; 361 | — |
| SECONDARY Participants From Time of Randomisation to All-cause Death |
375; 458 | — |
| SECONDARY Participants From Time of Randomisation to First Occurrence of an Expanded Composite CV Outcome Measure Consisting of: CV Death, Non-fatal MI, Non-fatal Stroke, Coronary Revascularisation or Unstable Angina Pectoris (UAP) Requiring Hospitalisation |
873; 1074 | — |
| SECONDARY Participants From Time of Randomisation to First Occurrence of a Composite Outcome Measure Consisting of: All-cause Death, Non-fatal MI, or Non-fatal Stroke |
710; 877 | — |
| SECONDARY Participants From Time of Randomisation to First Occurrence of Non-fatal MI |
234; 322 | — |
| SECONDARY Participants From Time of Randomisation to First Occurrence of Non-fatal Stroke |
154; 165 | — |
| SECONDARY Participants From Time of Randomisation to First Occurrence of Coronary Revascularisation |
473; 608 | — |
| SECONDARY Participants From Time of Randomisation to First Occurrence of UAP Requiring Hospitalisation |
109; 124 | — |
| SECONDARY Participants From Time of Randomisation to First Occurrence of HF Requiring Hospitalisation or Urgent HF Visit |
97; 122 | — |
| SECONDARY Participants From Time of Randomisation to First Occurrence of Glycosylated Haemoglobin (HbA1c) Greater Than Equals to (≥) 48 Millimole Per Mole (mmol/Mol) (6.5 Percentage [%]) |
306; 1059 | — |
| SECONDARY Participants From Time of Randomisation to First Occurrence of a 5-component Composite Nephropathy Outcome Measure |
155; 198 | — |
| SECONDARY Participants From Time of Randomisation to HbA1c ≥ 39 mmol/Mol (5.7%) (for Participants With a Screening HbA1c <39 mmol/Mol [5.7%]) |
623; 1501 | — |
| SECONDARY Participants With HbA1c < 39 mmol/Mol (5.7%) (for Participants With a Screening HbA1c ≥ 39 mmol/Mol [5.7%]) |
3363; 955; 3271; 978 | — |
| SECONDARY Change in Systolic Blood Pressure (SBP) |
-3.8; -0.6 | — |
| SECONDARY Change in Diastolic Blood Pressure (DBP) |
-1.1; -0.4 | — |
| SECONDARY Change in Pulse |
3.8; 0.9 | — |
| SECONDARY Change in High Sensitivity C-Reactive Protein (hsCRP) - Ratio to Baseline |
0.61; 1.00 | — |
| SECONDARY Change in Total Cholesterol - Ratio to Baseline |
0.95; 0.98 | — |
| SECONDARY Change in High Density Lipoprotein (HDL) Cholesterol - Ratio to Baseline |
1.05; 1.01 | — |
| SECONDARY Change in Low Density Lipoprotein (LDL) Cholesterol - Ratio to Baseline |
0.95; 0.97 | — |
| SECONDARY Change in Triglycerides - Ratio to Baseline |
0.82; 0.97 | — |
| SECONDARY Change in Body Weight |
-9.39; -0.87 | — |
| SECONDARY Change in Waist Circumference |
-7.5; -1.0 | — |
| SECONDARY Change From Randomisation (Week 0) in Participant Reported Outcome (PRO): EuroQol Five Dimensions Five Level Questionnaire (EQ-5D-5L) Index Score to Week 104 |
0.01; -0.01 | — |
| SECONDARY Change From Randomisation (Week 0) in PRO: EuroQol Five Dimensions Visual Analogue Scale (EQ-5D-VAS) to Week 104 |
2.38; 0.77 | — |
| SECONDARY Change in HbA1c - Percentage |
-0.31; 0.01 | — |
| SECONDARY Change in HbA1c - mmol/Mol |
-3.38; 0.10 | — |
Summary
The researchers are doing the study to see if semaglutide may reduce the risk of having cardiovascular events in patients with overweight or obesity and with prior cardiovascular disease. The participant will either get semaglutide (active medicine) or placebo ("dummy" medicine). Which treatment the participants get is decided by chance. The participant's chance of getting semaglutide or placebo is the same. The participant will get the study medicine in a pen. The participants will need to use the pen to inject the study medicine in a skinfold once a week. The study will last for about 2.5 to 5 years. Participants will have up to 25 clinic visits with the study doctor.
Eligibility Criteria
Inclusion Criteria
- Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
- Male or female, age greater than or equal to 45 years at the time of signing informed consent
- Body mass index (BMI) greater than or equal to 27 kg/m^2
- Have established cardiovascular (CV) disease as evidenced by at least one of the following: prior myocardial infarction; prior stroke (ischemic or haemorrhagic stroke); or symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with ankle-brachial index (ABI) less than 0.85 (at rest), or peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease
Exclusion Criteria
Cardiovascular-related:
- 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
- Presently classified as being in New York Heart Association (NYHA) Class IV heart failure
Glycaemia-related:
- HbA1c greater than or equal to 48 mmol/mol (6.5 %) as measured by the central laboratory at screening
- History of type 1 or type 2 diabetes (history of gestational diabetes is allowed)
- Treatment with glucose-lowering agents within 90 days before screening
- Treatment with any glucagon-like-peptide-1 receptor agonist (GLP-1 RA) within 90 days before screening
General safety:
- History or presence of chronic pancreatitis
- Presence of acute pancreatitis within the past 180 days prior to the day of screening
- Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
- End stage renal disease or chronic or intermittent haemodialysis or peritoneal dialysis
- Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed
- Severe psychiatric disorder which in the investigator's opinion could compromise compliance with the protocol
- Known or suspected hypersensitivity to trial products or related products
- Previous participation in this trial. Participation is defined as randomisation
- Receipt of any investigational medicinal product within 30 days before screening
- Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method
- Any disorder, unwillingness or inability, which in the investigator's opinion, might jeopardise the participant's safety or compliance with the protocol
Data sourced from ClinicalTrials.gov (NCT03574597). 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.