Phase 3
Completed N=3,183
A Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes
Source: ClinicalTrials.gov NCT02692716 ↗Enrolled (actual)
3,183
Serious AEs
20.7%
Results posted
Feb 2020
Primary outcomePrimary: Time From Randomisation to First Occurrence of a Major Adverse Cardiovascular Event (MACE) Composite Endpoint Consisting of: Cardiovascular Death, Non-fatal Myocardial Infarction or Non-fatal Stroke — 61; 76 Participants — p=< 0.0001
◆ Published Evidence
Highly cited
1,897citations · ~271 / year
Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.
Summary
This trial is conducted globally. The aim of the trial is to investigate the cardiovascular safety of oral semaglutide in subjects with type 2 diabetes.
Linked Publications (5)
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Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.
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Cardiovascular Outcomes Trials in Type 2 Diabetes: Where Do We Go From Here? Reflections From a <i>Diabetes Care</i> Editors' Expert Forum.
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Cardiovascular safety of oral semaglutide in patients with type 2 diabetes: Rationale, design and patient baseline characteristics for the PIONEER 6 trial.
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Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6.
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A population-adjusted indirect comparison of cardiovascular benefits of once-weekly subcutaneous semaglutide and dulaglutide in the treatment of patients with type 2 diabetes, with or without established cardiovascular disease.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time From Randomisation to First Occurrence of a Major Adverse Cardiovascular Event (MACE) Composite Endpoint Consisting of: Cardiovascular Death, Non-fatal Myocardial Infarction or Non-fatal Stroke |
61; 76 | < 0.0001 sig |
| SECONDARY Time From Randomisation to First Occurrence of an Expanded Composite Cardiovascular Endpoint Consisting of: Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke, UAP Requiring Hospitalisation or Hospitalisation for Heart Failure |
83; 100 | = 0.1827 |
| SECONDARY Time From Randomisation to First Occurrence of Each of the Individual Components in the Expanded Composite Cardiovascular Endpoint |
15; 30; 37; 31; 12; 16 | = 0.0261 sig |
| SECONDARY Time From Randomisation to First Occurrence of a Composite Endpoint Consisting of: All-cause Death, Non-fatal Myocardial Infarction or Nonfatal Stroke |
69; 89 | = 0.0952 |
| SECONDARY Time From Randomisation to First Occurrence of Fatal or Non-fatal Myocardial Infarction |
37; 35 | 0.8583 |
| SECONDARY Time From Randomisation to First Occurrence of Fatal or Non-fatal Stroke |
13; 17 | 0.4485 |
| SECONDARY Time From Randomisation to All-cause Death |
23; 45 | 0.0078 sig |
| SECONDARY Time to First AE Leading to Permanent Trial Product Discontinuation |
184; 104 | <0.0001 sig |
| SECONDARY Number of Serious Adverse Events |
545; 618 | — |
| SECONDARY Change in Eye Examination Category |
848; 843; 657; 673; 86; 74 | — |
| SECONDARY Change in Pulse Rate |
4; -0 | — |
| SECONDARY Change in Systolic and Diastolic Blood Pressure |
-5; -2; -1; -2 | — |
| SECONDARY Change in Glycosylated Haemoglobin (HbA1c) |
-1.0; -0.3 | — |
| SECONDARY Change in Body Weight |
-4.2; -0.8 | — |
| SECONDARY Change in Total Cholesterol - Ratio to Baseline |
0.97; 0.98 | — |
| SECONDARY Change in LDL-cholesterol - Ratio to Baseline |
0.96; 0.97 | — |
| SECONDARY Change in HDL-cholesterol - Ratio to Baseline |
1.05; 1.02 | — |
| SECONDARY Change in Triglycerides - Ratio to Baseline |
0.92; 0.97 | — |
Eligibility Criteria
Inclusion Criteria
- Male or female diagnosed with type 2 diabetes
- Age at least 50 years at screening and presence of cardiovascular disease, or age at least 60 years at screening and presence of at least one cardiovascular risk factor
Exclusion Criteria
- Current or previous (within 90 days prior to screening) treatment with any GLP-1 (glucagon-like peptide-1) receptor agonist, DPP-4 (dipeptidyl peptidase-4) inhibitor or pramlintide
- Family or personal history of multiple endocrine neoplasia type 2 (MEN 2) or medullary thyroid carcinoma (MTC)
- History of pancreatitis (acute or chronic)
- History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)
- Subjects presently classified as being in New York Heart Association (NYHA) Class IV heart failure
- Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
- Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 60 days prior to screening
- Chronic or intermittent hemodialysis or peritoneal dialysis or severe renal impairment (corresponding to eGFR (glomerular filtration rate, estimated) below 30 mL/min/1.73 m^2)
- History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ)
Data sourced from ClinicalTrials.gov (NCT02692716) and the linked publication. 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. Informational only — not medical advice.