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DiabetesPhase 3PIONEER 6NCT02692716

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

A Phase 3 study testing semaglutide in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 228 sites in 21 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
Diabetes, Diabetes Mellitus, Type 2
What is being tested?
semaglutide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
3,183 participants
Where
228 sitesin 21 countries
Study dates
17 Jan 2017to 25 Sep 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • 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)

Trial locations and contacts

228 sites in 21 countries.

228 sites in 21 countries

United States71 sites

  • Novo Nordisk Investigational Site

    Albany, New York, 12203

  • Novo Nordisk Investigational Site

    Albany, New York, 12206

  • Novo Nordisk Investigational Site

    Anderson, South Carolina, 29621

  • Novo Nordisk Investigational Site

    Arlington, Texas, 76012-4637

  • Novo Nordisk Investigational Site

    Asheville, North Carolina, 28803

  • Novo Nordisk Investigational Site

    Austin, Texas, 78705

  • Novo Nordisk Investigational Site

    Austin, Texas, 78731

  • Novo Nordisk Investigational Site

    Austin, Texas, 78749

  • Novo Nordisk Investigational Site

    Beaver, Pennsylvania, 15009

  • Novo Nordisk Investigational Site

    Boca Raton, Florida, 33433

  • Novo Nordisk Investigational Site

    Canton, Michigan, 48187

  • Novo Nordisk Investigational Site

    Chattanooga, Tennessee, 37404

  • Novo Nordisk Investigational Site

    Chattanooga, Tennessee, 37411

  • Novo Nordisk Investigational Site

    Cleveland, Ohio, 44195

  • Novo Nordisk Investigational Site

    Columbus, Ohio, 43203

  • Novo Nordisk Investigational Site

    Concord, California, 94520

  • Novo Nordisk Investigational Site

    Council Bluffs, Iowa, 51501

  • Novo Nordisk Investigational Site

    Dallas, Texas, 75230

  • Novo Nordisk Investigational Site

    Dallas, Texas, 75231

  • Novo Nordisk Investigational Site

    Dallas, Texas, 75390-9302

  • Novo Nordisk Investigational Site

    Fargo, North Dakota, 58104

  • Novo Nordisk Investigational Site

    Greenville, North Carolina, 27834

  • Novo Nordisk Investigational Site

    Honolulu, Hawaii, 96814

  • Novo Nordisk Investigational Site

    Huntington Beach, California, 92648

  • Novo Nordisk Investigational Site

    Hurst, Texas, 76054

  • Novo Nordisk Investigational Site

    Indianapolis, Indiana, 46254

  • Novo Nordisk Investigational Site

    Kingsport, Tennessee, 37660

  • Novo Nordisk Investigational Site

    Knoxville, Tennessee, 37938

  • Novo Nordisk Investigational Site

    La Jolla, California, 92037

  • Novo Nordisk Investigational Site

    La Mesa, California, 91942

  • Novo Nordisk Investigational Site

    Lancaster, California, 93534

  • Novo Nordisk Investigational Site

    Las Vegas, Nevada, 89128

  • Novo Nordisk Investigational Site

    Lexington, Kentucky, 40502

  • Novo Nordisk Investigational Site

    Lexington, Kentucky, 40503

  • Novo Nordisk Investigational Site

    Little Rock, Arkansas, 72211

  • Novo Nordisk Investigational Site

    Louisville, Kentucky, 40213

  • Novo Nordisk Investigational Site

    Maumee, Ohio, 43537

  • Novo Nordisk Investigational Site

    Michigan City, Indiana, 46360

  • Novo Nordisk Investigational Site

    Midland, Texas, 79707

  • Novo Nordisk Investigational Site

    Moncks Corner, South Carolina, 29461

  • Novo Nordisk Investigational Site

    Monroe, Louisiana, 71203

  • Novo Nordisk Investigational Site

    Monterey, California, 93940

  • Novo Nordisk Investigational Site

    Muncie, Indiana, 47304

  • Novo Nordisk Investigational Site

    Myrtle Beach, South Carolina, 29572

  • Novo Nordisk Investigational Site

    Nashua, New Hampshire, 03063

  • Novo Nordisk Investigational Site

    Nashville, Tennessee, 37203

  • Novo Nordisk Investigational Site

    Nashville, Tennessee, 37212

  • Novo Nordisk Investigational Site

    New Port Richey, Florida, 34652

  • Novo Nordisk Investigational Site

    Norfolk, Virginia, 23510-2015

  • Novo Nordisk Investigational Site

    North Massapequa, New York, 11758-1802

  • Novo Nordisk Investigational Site

    Omaha, Nebraska, 68114

  • Novo Nordisk Investigational Site

    Omaha, Nebraska, 68198

  • Novo Nordisk Investigational Site

    Philadelphia, Pennsylvania, 19114

  • Novo Nordisk Investigational Site

    Roswell, Georgia, 30076

  • Novo Nordisk Investigational Site

    Round Rock, Texas, 78681

  • Novo Nordisk Investigational Site

    San Antonio, Texas, 78220

  • Novo Nordisk Investigational Site

    San Antonio, Texas, 78228-6205

  • Novo Nordisk Investigational Site

    San Diego, California, 92111

  • Novo Nordisk Investigational Site

    San Ramon, California, 94583

  • Novo Nordisk Investigational Site

    Savannah, Georgia, 31406

  • Novo Nordisk Investigational Site

    Searcy, Arkansas, 72143

  • Novo Nordisk Investigational Site

    Slidell, Louisiana, 70461-4231

  • Novo Nordisk Investigational Site

    South Burlington, Vermont, 05403

  • Novo Nordisk Investigational Site

    Spartanburg, South Carolina, 29303

  • Novo Nordisk Investigational Site

    Springfield, Illinois, 62702

  • Novo Nordisk Investigational Site

    Troy, Michigan, 48098

  • Novo Nordisk Investigational Site

    Ventura, California, 93003

  • Novo Nordisk Investigational Site

    Waco, Texas, 76710

  • Novo Nordisk Investigational Site

    Westfield, New York, 14787

  • Novo Nordisk Investigational Site

    Wilmington, North Carolina, 28401

  • Novo Nordisk Investigational Site

    Winchester, Virginia, 22601-3834

Other trials in United States

India19 sites

  • Novo Nordisk Investigational Site

    Ahmedabad, Gujarat, 380006

  • Novo Nordisk Investigational Site

    Ahmedabad, Gujarat, 380052

  • Novo Nordisk Investigational Site

    Chennai, Tamil Nadu, 600086

  • Novo Nordisk Investigational Site

    Goa, Maharashtra, 403 202

  • Novo Nordisk Investigational Site

    Hyderabad, Andhra Pradesh, 500034

  • Novo Nordisk Investigational Site

    Hyderbad, Andhra Pradesh, 500 012

  • Novo Nordisk Investigational Site

    Kochi, Kerala, 682041

  • Novo Nordisk Investigational Site

    Kolkata, West Bengal, 700054

  • Novo Nordisk Investigational Site

    Kozhikode, Kerala, 673017

  • Novo Nordisk Investigational Site

    Ludhiana, Punjab, 141008

  • Novo Nordisk Investigational Site

    Mumbai, Maharashtra, 400008

  • Novo Nordisk Investigational Site

    Mumbai, Maharashtra, 400012

  • Novo Nordisk Investigational Site

    New Dehli, New Delhi, 110029

  • Novo Nordisk Investigational Site

    New Delhi, 110001

  • Novo Nordisk Investigational Site

    New Delhi, 110017

  • Novo Nordisk Investigational Site

    Pune, Maharashtra, 411001

  • Novo Nordisk Investigational Site

    Pune, Maharashtra, 411004

  • Novo Nordisk Investigational Site

    Pune, 411011

  • Novo Nordisk Investigational Site

    Thiruvananthapuram, Kerala, 695031

Other trials in India

Germany12 sites

  • Novo Nordisk Investigational Site

    Bochum, 44791

  • Novo Nordisk Investigational Site

    Dresden, 01307

  • Novo Nordisk Investigational Site

    Elsterwerda, 04910

  • Novo Nordisk Investigational Site

    Essen, 45219

  • Novo Nordisk Investigational Site

    Falkensee, 14612

  • Novo Nordisk Investigational Site

    Hamburg, 22607

  • Novo Nordisk Investigational Site

    Ludwigshafen, 67059

  • Novo Nordisk Investigational Site

    Münster, 48145

  • Novo Nordisk Investigational Site

    Oldenburg, 23758

  • Novo Nordisk Investigational Site

    Oldenburg I. Holst, 23758

  • Novo Nordisk Investigational Site

    Rehlingen-Siersburg, 66780

  • Novo Nordisk Investigational Site

    Saint Ingbert-Oberwürzbach, 66386

Other trials in Germany

Spain11 sites

  • Novo Nordisk Investigational Site

    Alcalá de Henares, 28805

  • Novo Nordisk Investigational Site

    Badalona, 08916

  • Novo Nordisk Investigational Site

    Fuenlabrada - Madrid, 28942

  • Novo Nordisk Investigational Site

    Madrid, 28046

  • Novo Nordisk Investigational Site

    Málaga, 29006

  • Novo Nordisk Investigational Site

    Palma de Mallorca, 07198

  • Novo Nordisk Investigational Site

    Pontevedra, 36071

  • Novo Nordisk Investigational Site

    Seville, 41003

  • Novo Nordisk Investigational Site

    Seville, 41010

  • Novo Nordisk Investigational Site

    Valencia, 46014

  • Novo Nordisk Investigational Site

    Valencia, 46026

Other trials in Spain

Turkey (Türkiye)11 sites

  • Novo Nordisk Investigational Site

    Ankara, 06100

  • Novo Nordisk Investigational Site

    Ankara, 06500

  • Novo Nordisk Investigational Site

    Antalya, 07058

  • Novo Nordisk Investigational Site

    Aydin, 09010

  • Novo Nordisk Investigational Site

    Denizli, 20070

  • Novo Nordisk Investigational Site

    Gaziantep, 27070

  • Novo Nordisk Investigational Site

    Istanbul, 34371

  • Novo Nordisk Investigational Site

    Istanbul, 34760

  • Novo Nordisk Investigational Site

    Izmir, 35100

  • Novo Nordisk Investigational Site

    Izmir, 35340

  • Novo Nordisk Investigational Site

    Rize, 53020

Other trials in Turkey (Türkiye)

Malaysia10 sites

  • Novo Nordisk Investigational Site

    Ipoh, Perak, 30990

  • Novo Nordisk Investigational Site

    Kota Bharu, 15586

  • Novo Nordisk Investigational Site

    Kota Bharu, Kelantan, 16150

  • Novo Nordisk Investigational Site

    Kota Samarahan, 94300

  • Novo Nordisk Investigational Site

    Kuala Lumpur, 50400

  • Novo Nordisk Investigational Site

    Kuala Lumpur, 59100

  • Novo Nordisk Investigational Site

    Kuching, 93586

  • Novo Nordisk Investigational Site

    Malacca, 75400

  • Novo Nordisk Investigational Site

    Putrajaya, 62250

  • Novo Nordisk Investigational Site

    Seremban, 70300

Other trials in Malaysia

South Africa9 sites

  • Novo Nordisk Investigational Site

    Bloemfontein, Free State, 9301

  • Novo Nordisk Investigational Site

    Cape Town, Western Cape, 7925

  • Novo Nordisk Investigational Site

    Durban, KwaZulu-Natal, 4001

  • Novo Nordisk Investigational Site

    Durban, KwaZulu-Natal, 4450

  • Novo Nordisk Investigational Site

    Johannesburg, Gauteng, 1827

  • Novo Nordisk Investigational Site

    Johannesburg, Gauteng, 2013

  • Novo Nordisk Investigational Site

    Lenasia, Gauteng, 1827

  • Novo Nordisk Investigational Site

    Middleburg, Mpumalanga, 1055

  • Novo Nordisk Investigational Site

    Pretoria, Gauteng, 0181

Other trials in South Africa

United Kingdom9 sites

  • Novo Nordisk Investigational Site

    Aberdeen, AB25 2ZD

  • Novo Nordisk Investigational Site

    Bristol, BS10 5NB

  • Novo Nordisk Investigational Site

    Dundee, DD1 9SY

  • Novo Nordisk Investigational Site

    Edinburgh, EH4 2XU

  • Novo Nordisk Investigational Site

    Exeter, EX2 5DW

  • Novo Nordisk Investigational Site

    Guildford, GU2 7XX

  • Novo Nordisk Investigational Site

    Norfolk, NR4 7UQ

  • Novo Nordisk Investigational Site

    Swansea, SA2 8PP

  • Novo Nordisk Investigational Site

    Watford, WD18 0HB

Other trials in United Kingdom

Israel8 sites

  • Novo Nordisk Investigational Site

    Haifa, 35152

  • Novo Nordisk Investigational Site

    Holon, 58100

  • Novo Nordisk Investigational Site

    Jerusalem, 91120

  • Novo Nordisk Investigational Site

    Nahariya, 22100

  • Novo Nordisk Investigational Site

    Petah Tikva, 49100

  • Novo Nordisk Investigational Site

    Rishon LeZiyyon, 75650

  • Novo Nordisk Investigational Site

    Tel Aviv, 64239

  • Novo Nordisk Investigational Site

    Tel Aviv, 6937947

Other trials in Israel

Romania8 sites

  • Novo Nordisk Investigational Site

    Bucharest, 010507

  • Novo Nordisk Investigational Site

    Bucharest, 010627

  • Novo Nordisk Investigational Site

    Bucharest, 020359

  • Novo Nordisk Investigational Site

    Bucharest, 020475

  • Novo Nordisk Investigational Site

    Bucharest

  • Novo Nordisk Investigational Site

    Galati, 800098

  • Novo Nordisk Investigational Site

    Oradea, Bihor County, 410025

  • Novo Nordisk Investigational Site

    Târgu Mureş, Mureș County, 540142

Other trials in Romania

Argentina7 sites

  • Novo Nordisk Investigational Site

    Buenos Aires, B1704ETD

  • Novo Nordisk Investigational Site

    Buenos Aires, C1428ART

  • Novo Nordisk Investigational Site

    CABA, C1120AAC

  • Novo Nordisk Investigational Site

    CABA, C1428ART

  • Novo Nordisk Investigational Site

    CABA, C1440AAD

  • Novo Nordisk Investigational Site

    Córdoba, 5000

  • Novo Nordisk Investigational Site

    Lanús Este, B1824KAJ

Other trials in Argentina

Canada7 sites

  • Novo Nordisk Investigational Site

    Brampton, Ontario, L6T 0G1

  • Novo Nordisk Investigational Site

    Brampton, Ontario, L6Z 4N5

  • Novo Nordisk Investigational Site

    Calgary, Alberta, T2V 4J2

  • Novo Nordisk Investigational Site

    Concord, Ontario, L4K 4M2

  • Novo Nordisk Investigational Site

    Edmonton, Alberta, T6H 2L4

  • Novo Nordisk Investigational Site

    Montreal, Quebec, H4A 3T2

  • Novo Nordisk Investigational Site

    Toronto, Ontario, M5G 2C4

Other trials in Canada

Italy7 sites

  • Novo Nordisk Investigational Site

    Bergamo, 24127

  • Novo Nordisk Investigational Site

    Catanzaro, 88100

  • Novo Nordisk Investigational Site

    Chieti, 66100

  • Novo Nordisk Investigational Site

    Milan, 20132

  • Novo Nordisk Investigational Site

    Palermo, 90127

  • Novo Nordisk Investigational Site

    Roma, 00133

  • Novo Nordisk Investigational Site

    Roma, 00161

Other trials in Italy

Mexico6 sites

  • Novo Nordisk Investigational Site

    Guadalajara, Jalisco, 44600

  • Novo Nordisk Investigational Site

    Guadalajara, Jalisco, 44650

  • Novo Nordisk Investigational Site

    Guadalajara, Jalisco, 44670

  • Novo Nordisk Investigational Site

    Mérida, Yucatán, 97070

  • Novo Nordisk Investigational Site

    Monterrey, Nuevo León, 64460

  • Novo Nordisk Investigational Site

    San Luis Potosí City, 78200

Other trials in Mexico

Thailand6 sites

  • Novo Nordisk Investigational Site

    Bangkok, 10330

  • Novo Nordisk Investigational Site

    Bangkok, 10400

  • Novo Nordisk Investigational Site

    Bangkok, 10700

  • Novo Nordisk Investigational Site

    Chiang Mai, 50200

  • Novo Nordisk Investigational Site

    Klong Luang, Pathumthani, 12120

  • Novo Nordisk Investigational Site

    Nakhon Ratchasima, 30000

Other trials in Thailand

Denmark5 sites

  • Novo Nordisk Investigational Site

    Aarhus N, 8200

  • Novo Nordisk Investigational Site

    Esbjerg, 6700

  • Novo Nordisk Investigational Site

    Hellerup, 2900

  • Novo Nordisk Investigational Site

    Hvidovre, 2650

  • Novo Nordisk Investigational Site

    Odense, 5000

Other trials in Denmark

Netherlands5 sites

  • Novo Nordisk Investigational Site

    Almere Stad, 1311RL

  • Novo Nordisk Investigational Site

    Amsterdam, 1066 EC

  • Novo Nordisk Investigational Site

    Eindhoven, 5631 BM

  • Novo Nordisk Investigational Site

    Hoogeveen, 7909 AA

  • Novo Nordisk Investigational Site

    Nijmegen, 6525 GA

Other trials in Netherlands

Poland5 sites

  • Novo Nordisk Investigational Site

    Krakow, 31-261

  • Novo Nordisk Investigational Site

    Krakow, 31-271

  • Novo Nordisk Investigational Site

    Lublin, 20-044

  • Novo Nordisk Investigational Site

    Poznan, 60-589

  • Novo Nordisk Investigational Site

    Warsaw, 01-192

Other trials in Poland

Algeria4 sites

  • Novo Nordisk Investigational Site

    Annaba, 23000

  • Novo Nordisk Investigational Site

    Oran, 31000

  • Novo Nordisk Investigational Site

    Sétif, 19000

  • Novo Nordisk Investigational Site

    Tizi Ouzou, 16015

Other trials in Algeria

Brazil4 sites

  • Novo Nordisk Investigational Site

    Curitiba, Paraná, 80030-110

  • Novo Nordisk Investigational Site

    Mogi das Cruzes, São Paulo, 08780-090

  • Novo Nordisk Investigational Site

    São José dos Campos, São Paulo, 12243-280

  • Novo Nordisk Investigational Site

    São Paulo, São Paulo, 01228-200

Other trials in Brazil

Taiwan4 sites

  • Novo Nordisk Investigational Site

    Kaohsiung City, 833

  • Novo Nordisk Investigational Site

    Taichung, 407

  • Novo Nordisk Investigational Site

    Tainan, 710

  • Novo Nordisk Investigational Site

    Taipei, 100

Other trials in Taiwan

About this study

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.

Being tested
semaglutide, placebo
Medical subject headings
Diabetes Mellitus, Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • semaglutideDrug

    For oral use once daily.

  • placeboDrug

    For oral use once daily.

Study groups in NCT02692716
Study groupRoleWhat they receive
Oral semaglutideExperimentalNot described
Receives: Drug: semaglutide
PlaceboPlacebo comparatorNot described
Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Number of participants experiencing a first event of a MACE, defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

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

Secondary outcomes (17)

  1. 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

    Participants experiencing first occurrence of an expanded composite CV endpoint [defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, UAP (unstable angina pectoris) requiring hospitalisation or heart failure requiring hospitalisation] are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

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

  2. Time From Randomisation to First Occurrence of Each of the Individual Components in the Expanded Composite Cardiovascular Endpoint

    Participants experiencing an event onset for each individual component of the expanded composite cardiovascular outcomes (defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, unstable angina requiring hospitalisation or heart failure requiring hospitalisation) are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

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

  3. Time From Randomisation to First Occurrence of a Composite Endpoint Consisting of: All-cause Death, Non-fatal Myocardial Infarction or Nonfatal Stroke

    Participants experiencing first occurrence of a composite CV endpoint (defined as all-cause death, non-fatal myocardial infarction or nonfatal stroke) are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

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

  4. Time From Randomisation to First Occurrence of Fatal or Non-fatal Myocardial Infarction

    Number of participants experiencing a first event of a fatal or non-fatal myocardial infarction are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

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

  5. Time From Randomisation to First Occurrence of Fatal or Non-fatal Stroke

    Number of participants experiencing a first event of a fatal or non-fatal stroke are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

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

  6. Time From Randomisation to All-cause Death

    Number of all-cause deaths in the study are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

    Measured: Maximum treatment duration is dependent on event rates and is expected to be no longer than 19 months + 5 weeks of follow-up period.

  7. Time to First AE Leading to Permanent Trial Product Discontinuation

    Number of participants who permanently discontinued trial product in ths study are presented. Results are based on the on-treatment observation period which starts at the date of first dose on trial product; ends on last date on trial product +38 days (ascertainment window).

    Measured: Maximum treatment duration is dependent on event rates and is expected to be no longer than 19 months + 38 days of ascertainment window.

  8. Number of Serious Adverse Events

    Number of serious adverse events were recorded from week 0 to week 87 in the study. Results are based on the on-treatment observation period which started at the date of first dose on trial product and ended on last date on trial product +38 days (ascertainment window).

    Measured: Maximum treatment duration is dependent on event rates and is expected to be no longer than 19 months + 38 days of ascertainment window.

  9. Change in Eye Examination Category

    Participants with eye examination findings, normal, abnormal non clinically significant (NCS) and abnormal clinically significant (CS) at baseline (week -3) and end of treatment visit (week 83) are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

    Measured: Week -3, End of treatment

  10. Change in Pulse Rate

    Change from baseline (week 0) in pulse rate measured at the end of treatment visit (week 83) is reported. Results are based on the on-treatment observation period which started at the date of first dose on trial product, ended on last date on trial product +38 days (ascertainment window).

    Measured: Week 0, End of treatment

  11. Change in Systolic and Diastolic Blood Pressure

    Change from baseline (week 0) in systolic and diastolic blood pressure measured at the end of treatment visit (week 83) is reported. Results are based on the on-treatment observation period which started at the date of first dose on trial product, ended on last date on trial product +38 days (ascertainment window).

    Measured: Week 0, End of treatment

  12. Change in Glycosylated Haemoglobin (HbA1c)

    Change from baseline (week 0) in HbA1c measured at the end of treatment visit (week 83) is reported. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

    Measured: Week 0, End of treatment

  13. Change in Body Weight

    Change from baseline (week 0) in body weight measured at the end of treatment visit (week 83) is reported. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

    Measured: Week 0, End of treatment

  14. Change in Total Cholesterol - Ratio to Baseline

    Change from baseline (week 0) in total cholesterol (mmol/L) at the end of treatment (week 83) visit is presented as ratio to baseline. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

    Measured: Week 0, End of treatment

  15. Change in LDL-cholesterol - Ratio to Baseline

    Change from baseline (week 0) in LDL cholesterol (mmol/L) at end of treatment visit (week 83) is presented as ratio to baseline. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

    Measured: Week 0, End of treatment

  16. Change in HDL-cholesterol - Ratio to Baseline

    Change from baseline (week 0) in HDL cholesterol (mmol/L) at end of treatment visit (week 83) is presented as ratio to baseline. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

    Measured: Week 0, End of treatment

  17. Change in Triglycerides - Ratio to Baseline

    Change from baseline (week 0) in triglycerides (mmol/L) at end of treatment visit (week 83) is presented as ratio to baseline. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

    Measured: Week 0, End of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Feb 2016 (estimated)
  2. Study start17 Jan 2017
  3. Primary completion25 Sep 2018
  4. Study completion25 Sep 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
3,183 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02692716
Sponsor's protocol ID
NN9924-4221
Other IDs
2015-003563-10, U1111-1173-0750, NL56580.091.16, 2015
Acronym
PIONEER 6
Status last verified
Jul 2022
First submitted
23 Feb 2016
Last updated
20 Jul 2022
Data monitoring committee
No

Publications

  • Cefalu WT, Kaul S, Gerstein HC, Holman RR, Zinman B, Skyler JS, Green JB, Buse JB, Inzucchi SE, Leiter LA, Raz I, Rosenstock J, Riddle MC. Cardiovascular Outcomes Trials in Type 2 Diabetes: Where Do We Go From Here? Reflections From a Diabetes Care Editors' Expert Forum. Diabetes Care. 2018 Jan;41(1):14-31. doi: 10.2337/dci17-0057.

    PubMed 29263194

  • Bain SC, Mosenzon O, Arechavaleta R, Bogdanski P, Comlekci A, Consoli A, Deerochanawong C, Dungan K, Faingold MC, Farkouh ME, Franco DR, Gram J, Guja C, Joshi P, Malek R, Merino-Torres JF, Nauck MA, Pedersen SD, Sheu WH, Silver RJ, Tack CJ, Tandon N, Jeppesen OK, Strange M, Thomsen M, Husain M. Cardiovascular safety of oral semaglutide in patients with type 2 diabetes: Rationale, design and patient baseline characteristics for the PIONEER 6 trial. Diabetes Obes Metab. 2019 Mar;21(3):499-508. doi: 10.1111/dom.13553. Epub 2018 Nov 11.

    PubMed 30284349

  • Husain M, Birkenfeld AL, Donsmark M, Dungan K, Eliaschewitz FG, Franco DR, Jeppesen OK, Lingvay I, Mosenzon O, Pedersen SD, Tack CJ, Thomsen M, Vilsboll T, Warren ML, Bain SC; PIONEER 6 Investigators. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2019 Aug 29;381(9):841-851. doi: 10.1056/NEJMoa1901118. Epub 2019 Jun 11.

    PubMed 31185157

  • Evans LM, Mellbin L, Johansen P, Lawson J, Paine A, Sandberg A. 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. Endocrinol Diabetes Metab. 2021 May 15;4(3):e00259. doi: 10.1002/edm2.259. eCollection 2021 Jul.

    PubMed 34277983

  • Husain M, Consoli A, De Remigis A, Pettersson Meyer AS, Rasmussen S, Bain S. Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6. Cardiovasc Diabetol. 2022 Apr 28;21(1):64. doi: 10.1186/s12933-022-01489-6.

    PubMed 35484580

  • Aroda VR, Bauer R, Christiansen E, Haluzik M, Kallenbach K, Montanya E, Rosenstock J, Meier JJ. Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. Diabetes Obes Metab. 2022 Jul;24(7):1338-1350. doi: 10.1111/dom.14710. Epub 2022 May 9.

    PubMed 35373893

  • Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.

    PubMed 39963952

  • Bain SC, Belmar N, Hoff ST, Husain M, Rasmussen S, Vilsboll T, Petrie MC. Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN 6 and PIONEER 6. Diabetes Ther. 2025 Jan;16(1):15-28. doi: 10.1007/s13300-024-01659-7. Epub 2024 Nov 9.

    PubMed 39520501

  • Rossing P, Bain SC, Bosch-Traberg H, Sokareva E, Heerspink HJL, Rasmussen S, Mellbin LG. Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis. Cardiovasc Diabetol. 2023 Aug 24;22(1):220. doi: 10.1186/s12933-023-01949-7.

    PubMed 37620807

  • Strain WD, Frenkel O, James MA, Leiter LA, Rasmussen S, Rothwell PM, Sejersten Ripa M, Truelsen TC, Husain M. Effects of Semaglutide on Stroke Subtypes in Type 2 Diabetes: Post Hoc Analysis of the Randomized SUSTAIN 6 and PIONEER 6. Stroke. 2022 Sep;53(9):2749-2757. doi: 10.1161/STROKEAHA.121.037775. Epub 2022 May 18.

    PubMed 35582947

  • Verma S, Fainberg U, Husain M, Rasmussen S, Ryden L, Ripa MS, Buse JB. Applying REWIND cardiovascular disease criteria to SUSTAIN 6 and PIONEER 6: An exploratory analysis of cardiovascular outcomes with semaglutide. Diabetes Obes Metab. 2021 Jul;23(7):1677-1680. doi: 10.1111/dom.14360. Epub 2021 Mar 18.

    PubMed 33606902

  • Husain M, Bain SC, Holst AG, Mark T, Rasmussen S, Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. Cardiovasc Diabetol. 2020 Sep 30;19(1):156. doi: 10.1186/s12933-020-01106-4.

    PubMed 32998732

  • Thethi TK, Pratley R, Meier JJ. Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme. Diabetes Obes Metab. 2020 Aug;22(8):1263-1277. doi: 10.1111/dom.14054. Epub 2020 May 13.

    PubMed 32267058

  • Husain M, Bain SC, Jeppesen OK, Lingvay I, Sorrig R, Treppendahl MB, Vilsboll T. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab. 2020 Mar;22(3):442-451. doi: 10.1111/dom.13955. Epub 2020 Feb 5.

    PubMed 31903692

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing semaglutide in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 228 sites in 21 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 228 sites in United States, India, Germany, Spain, Turkey (Türkiye) and 16 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02692716, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2022; AzTrials last refreshed its copy on 8 Nov 2026.

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