Phase 3 · Semaglutide

PIONEER 6 trial results

A Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes

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 (Participants), Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period.. Oral Semaglutide: 61; Placebo: 76.

Participants: 3,183
Status: completed
Completed: 2018-09-25
Sponsor: Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT02692716), updated at source Jul 20, 2022. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What PIONEER 6 measured first

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 StrokeParticipants · Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period. · count of participants

Oral Semaglutiden=1,591	Placebon=1,592
61	76

Secondary outcomes

What else it measured

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 FailureParticipants · Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period. · count of participants

Oral Semaglutiden=1,591	Placebon=1,592
83	100

Time From Randomisation to First Occurrence of Each of the Individual Components in the Expanded Composite Cardiovascular EndpointParticipants · Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period. · count of participants

Measure	Oral Semaglutiden=1,591	Placebon=1,592
Cardiovascular death	15	30
Non-fatal myocardial infarction	37	31
Non-fatal stroke	12	16
Unstable angina requiring hospitalisation	11	7
Heart failure requiring hospitalisation	21	24

Time From Randomisation to First Occurrence of a Composite Endpoint Consisting of: All-cause Death, Non-fatal Myocardial Infarction or Nonfatal StrokeParticipants · Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period. · count of participants

Oral Semaglutiden=1,591	Placebon=1,592
69	89

Time From Randomisation to First Occurrence of Fatal or Non-fatal Myocardial InfarctionParticipants · Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period. · count of participants

Oral Semaglutiden=1,591	Placebon=1,592
37	35

Time From Randomisation to First Occurrence of Fatal or Non-fatal StrokeParticipants · Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period. · count of participants

Oral Semaglutiden=1,591	Placebon=1,592
13	17

Time From Randomisation to All-cause DeathParticipants · Maximum treatment duration is dependent on event rates and is expected to be no longer than 19 months + 5 weeks of follow-up period. · count of participants

Oral Semaglutiden=1,591	Placebon=1,592
23	45

Time to First AE Leading to Permanent Trial Product DiscontinuationParticipants · Maximum treatment duration is dependent on event rates and is expected to be no longer than 19 months + 38 days of ascertainment window. · count of participants

Oral Semaglutiden=1,591	Placebon=1,592
184	104

Number of Serious Adverse EventsEvents · Maximum treatment duration is dependent on event rates and is expected to be no longer than 19 months + 38 days of ascertainment window. · number

Oral Semaglutiden=1,591	Placebon=1,592
545	618

Change in Eye Examination CategoryParticipants · Week -3, End of treatment · count of participants

Measure	Oral Semaglutiden=1,591	Placebon=1,592
Left eye fundoscopy (week -3): Normal	848	843
Left eye fundoscopy (week -3): Abnormal NCS	657	673
Left eye fundoscopy (week -3): Abnormal CS	86	74
Right eye fundoscopy (week -3): Normal	845	858
Right eye fundoscopy (week -3): Abnormal NCS	659	661
Right eye fundoscopy (week -3): Abnormal CS	86	72
Left eye fundoscopy (EOT): Normal	783	790
Left eye fundoscopy (EOT): Abnormal NCS	599	597
Left eye fundoscopy (EOT): Abnormal CS	83	62
Right eye fundoscopy (EOT): Normal	780	787
Right eye fundoscopy (EOT): Abnormal NCS	601	599
Right eye fundoscopy (EOT): Abnormal CS	81	64

Change in Pulse RateBeats/minute · Week 0, End of treatment · mean

Oral Semaglutiden=1,345	Placebon=1,411
4(11)	-0(11)

Change in Systolic and Diastolic Blood PressuremmHg · Week 0, End of treatment · mean

Measure	Oral Semaglutiden=1,345	Placebon=1,411
Systolic blood pressure	-5(18)	-2(18)
Diastolic blood pressure	-1(11)	-2(10)

Change in Glycosylated Haemoglobin (HbA1c)Percentage of HbA1c · Week 0, End of treatment · mean

Oral Semaglutiden=1,489	Placebon=1,473
-1.0(1.4)	-0.3(1.3)

The trial

How PIONEER 6 was run

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.

Oral semaglutide
Placebo

Who could join the trial

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)

Published papers

Papers from PIONEER 6

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

GLPcompare is an informational data platform, not a medical provider or pharmacy. Nothing here is medical advice, a diagnosis, or a recommendation to start, stop, or change any treatment. Data is aggregated from public sources and can be incomplete or out of date. Always confirm with a licensed clinician and the current FDA label.