AzTrials
AzTrials

Diabetes Mellitus, Type 2Phase 3PIONEER PLUSNCT04707469

Research Study to Compare Three Doses of Semaglutide Tablets Taken Once Daily in People With Type 2 Diabetes

A Phase 3 study testing Oral semaglutide in people with Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 228 sites in 15 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 study compares three doses of once daily semaglutide tablets in people with type 2 diabetes who were previously treated with other oral anti-diabetic medicines. Participants will be initiated on the lowest starting dose of 3 mg and gradually increased until they reach the final trial dose of 14 mg, 25 mg or 50 mg… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diabetes Mellitus, Type 2
What is being tested?
Oral semaglutide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,606 participants
Where
228 sitesin 15 countries
Study dates
15 Jan 2021to 8 Mar 2023
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female, age above or equal to 18 years at the time of signing informed consent.
  • Diagnosed with type 2 diabetes mellitus at least 180 days prior to the day of screening.
  • HbA1c of 8.0-10.5% (64-91 mmol/mol) (both inclusive).
  • BMI equal to or above 25 kg/m^2
  • Stable daily dose(s) for 90 days prior to the day of screening of any of the following treatment regimens:
  • No more than 3 of the following oral anti-diabetic drugs and at least 1 marked with a *:
Show all 11Show fewer
  • Metformin (equal to or above1500 mg or maximum tolerated or effective dose).
  • Sulfonylureas (SU) (equal to or above half of the maximum approved dose according to local label or maximum tolerated or effective dose).
  • Sodium/glucose cotransporter 2 (SGLT2) inhibitors (maximum tolerated dose).
  • Dipeptidyl peptidase-4 (DPP-4) inhibitors (maximally indicated dose as per local label).
  • Subjects, on treatment with stable dose of DPP-4 inhibitors at inclusion, must be willing to discontinue DPP-4 inhibitor treatment at randomisation (with no wash-out).

Who cannot join

  • Treatment with any medication indicated for the treatment of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed.
  • Renal impairment measured as estimated glomerular filtration rate (eGFR) value of below 30 mL/min/1.73 m^2 according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation as defined by kidney disease improving global outcomes (KDIGO 2012) classification.
  • Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Trial locations and contacts

228 sites in 15 countries.

228 sites in 15 countries

United States84 sites
  • Arlington Family Res. Ctr Inc

    Arlington, Texas, 76012-4637

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • Pennington Biom Res Ctr

    Baton Rouge, Louisiana, 70808

  • Elite Clinical Trials

    Blackfoot, Idaho, 83221

  • Brigham & Women's Hospital

    Boston, Massachusetts, 02115-5804

  • Holston Medical Group Pc

    Bristol, Tennessee, 37620-7352

  • American Clinical Trials

    Buena Park, California, 90620

  • Mercury Str Med Grp, PLLC

    Butte, Montana, 59701

  • UNC Diabetes Care Center_Chapel Hill

    Chapel Hill, North Carolina, 27514

  • Chattanooga Medical Research, LLC

    Chattanooga, Tennessee, 37404

  • Cedar-Crosse Research Center

    Chicago, Illinois, 60607

  • Rapid Medical Research Inc

    Cleveland, Ohio, 44122

  • Optumcare Clinical Trials,LLC-Golden

    Colorado Springs, Colorado, 80906

  • Alliance for Multispec Res

    Coral Gables, Florida, 33134

  • Corvallis Clinic PC Clinical Research Department

    Corvallis, Oregon, 97330-3737

  • Velocity Clinical Res-Dallas

    Dallas, Texas, 75230

  • Velocity Clinical Research, Dallas

    Dallas, Texas, 75230

  • UT Southwestern Med Cntr

    Dallas, Texas, 75390-9302

  • Lillestol Research LLC

    Fargo, North Dakota, 58104

  • Aa Mrc Llc

    Flint, Michigan, 48504

  • Care United Research, LLC

    Forney, Texas, 75126

  • Prestige Clinical Research

    Franklin, Ohio, 45005

  • Valley Research

    Fresno, California, 93720

  • Macoupin Research Group

    Gillespie, Illinois, 62033

  • PharmQuest Life Sciences LLC

    Greensboro, North Carolina, 27408

  • Palmetto Clinical Research

    Greenville, South Carolina, 29615

  • East West Med Res Inst

    Honolulu, Hawaii, 96814

  • JCCT- Juno NW Houston

    Houston, Texas, 77040

  • JCCT- Juno NW Houston

    Houston, Texas, 77074

  • Southwest Clinical Trials

    Houston, Texas, 77074

  • Family Practice Care Associates

    Humble, Texas, 77338

  • Research Trials Worldwide LLC

    Humble, Texas, 77338

  • Murphy Research Center

    Humboldt, Tennessee, 38343

  • Rocky Mt Clin Res, LLC

    Idaho Falls, Idaho, 83404-7596

  • Midwest Inst For Clin Res

    Indianapolis, Indiana, 46260

  • Northeast Research Institute

    Jacksonville, Florida, 32204

  • Juno Research, LLC_Cary

    Katy, Texas, 77450

  • Velocity Clin Res San Diego

    La Mesa, California, 91942

  • Centex Studies, Inc._Lake Charles

    Lake Charles, Louisiana, 70601

  • First Valley Medical Group

    Lancaster, California, 93534

  • The Research Group of Lexington LLC

    Lexington, Kentucky, 40503

  • DCOL Ctr for Clin Res

    Longview, Texas, 75605

  • Pacific Clinical Studies

    Los Alamitos, California, 90720

  • Velocity Clin Res Los Angeles

    Los Angeles, California, 90017

  • L-MARC Research Center

    Louisville, Kentucky, 40213

  • Albert J Weisbrot

    Mason, Ohio, 45040

  • Clinical Neuroscience Solutions

    Memphis, Tennessee, 38119

  • Solaris Clinical Research

    Meridian, Idaho, 83646

  • San Marcus Res Clin Miami Lakes

    Miami Lakes, Florida, 33014

  • Health Res of Hampton Roads

    Newport News, Virginia, 23606

  • York Clinical Research LLC

    Norfolk, Virginia, 23504

  • Intend Research

    Norman, Oklahoma, 73069

  • Diabetes Medical Center Of California

    Northridge, California, 91325

  • Capital Clin Res Ctr,LLC

    Olympia, Washington, 98502

  • Univ of Nebraska Medical CTR

    Omaha, Nebraska, 68198-3020

  • University of Nebraska Medical Center-Diabetes Center

    Omaha, Nebraska, 68198-4120

  • Complete Health Research

    Ormond Beach, Florida, 32174-6302

  • MD Medical Research

    Oxon Hill, Maryland, 20745

  • Desert Oasis Hlthcr Med Group

    Palm Springs, California, 92262

  • UnityPoint Health-Diabetes Care Center

    Peoria, Illinois, 61603

  • Preferred Primary Care Physicians_Pittsburgh

    Pittsburgh, Pennsylvania, 15236

  • Research Institute Of Dallas

    Plano, Texas, 75093

  • Clinical Trial Res Assoc,Inc

    Plantation, Florida, 33324

  • Progressive Medical Research

    Port Orange, Florida, 32127

  • Gateway Research Center

    Poway, California, 92064

  • Dominion Medical Associates

    Richmond, Virginia, 23219

  • Endo Res Solutions Inc

    Roswell, Georgia, 30076

  • VIP Trials

    San Antonio, Texas, 78230

  • VIP Trials

    San Antonio, Texas, 78231

  • Consano Clinical Research, LLC

    Shavano Park, Texas, 78231

  • Evanston Premier Hlthcr Res

    Skokie, Illinois, 60077

  • Encompass Clinical Research_Spring Valley

    Spring Valley, California, 91978

  • Simcare Medical Research, LLC

    Sugar Land, Texas, 77478

  • Palmetto Clinical Research

    Summerville, South Carolina, 29485

  • Cotton O'Neil Diab & Endo Ctr

    Topeka, Kansas, 66606

  • Premier Research Inc.

    Trenton, New Jersey, 08611

  • Arcturus Healthcare, PLC.

    Troy, Michigan, 48098

  • Diablo Clinical Research, Inc.

    Walnut Creek, California, 94598

  • MassResearch, LLC

    Waltham, Massachusetts, 02453

  • Chase Medical Research LLC

    Waterbury, Connecticut, 06708

  • Wenatchee Valley Hospital and Clinics

    Wenatchee, Washington, 98801-2028

  • Iowa Diab & Endo Res Center

    West Des Moines, Iowa, 50266

  • San Fernando Valley Hlth Inst, LLC

    West Hills, California, 91304

  • Accellacare

    Wilmington, North Carolina, 28401

Other trials in United States

India25 sites
  • Ramaiah Memorial Hospital

    Bangalore, Karnataka, 560054

  • Belgaum Diabetes Centre

    Belagavi, Karnataka, 590001

  • KLES & Prabhakar Kore Hospital and Research Centre

    Belagavi, Karnatka, 590010

  • Apollo Hospital

    Delhi, New Delhi, 110076

  • Endolife Specialty Hospitals

    Guntur, Andhra Pradesh, 522001

  • Care Outpatient Centre

    Hyderabad, Andhra Pradesh, 500034

  • Gandhi Hospital & Medical college

    Hyderabad, Telangana, 500003

  • Gleneagles Hospitals

    Hyderabad, Telangana, 500004

  • Osmania General Hospital

    Hyderabad, Telangana, 500012

  • Amrita Institute Of Medical Sciences & Research Centre

    Kochi, Kerala, 682041

  • I.P.G.M.E & R Hospital

    Kolkata, West Bengal, 700020

  • Apollo Multispeciality Hospital, Kolkata

    Kolkata, West Bengal, 700054

  • Kurnool Medical Collage

    Kurnool, Andhra Pradesh, 518002

  • MV Hospital and Research Centre

    Lucknow, Uttar Pradesh, 226003

  • Dayanand Medical College & Hospital

    Ludhiana, Punjab, 141001

  • Seth GS medical college and KEM Hospital

    Mumbai, Maharashtra, 400012

  • Apollo Hospital, Navi Mumbai

    Mumbai, Maharashtra, 400614

  • All India Institute of Medical Sciences

    New Dehli, New Delhi, 110029

  • Fortis Hospital, Shalimar Bagh, New Delhi

    New Delhi, National Capital Territory of Delhi, 110088

  • Deenanath Mangeshkar Hospital & Research Centre

    Pune, Maharashtra, 411004

  • Deenanath Mangeshkar Hospital and Research Centre

    Pune, Maharashtra, 411004

  • Inamdar Multispeciality Hospital

    Pune, Maharashtra, 411040

  • PGIMS Rohtak

    Rohtak, Haryana, 124001

  • Nirmal Hospital Pvt. Ltd.

    Surat, Gujarat, 395002

  • Christian Medical College Hospital, Vellore

    Vellore, Tamil Nadu, 632004

Other trials in India

Poland21 sites
  • Uniwersytecki Szpital Kliniczny w Bialymstoku

    Bialystok, Podlaskie Voivodeship, 15-276

  • NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny Małgorzata Arciszewska

    Bialystok, Podlaskie Voivodeship, 15-435

  • Kresmed Sp. z o. o.

    Bialystok, Podlaskie Voivodeship, 15-481

  • Uniwersytecki Szpital Kliniczny w Bialymstoku

    Bialystok, 15-276

  • Osteo Medic s.c. Artur Racewicz Jerzy Supronik

    Bialystok, 15-351

  • SNZOZ Lege Artis

    Bialystok, 15-404

  • Centrum Kliniczno Badawcze

    Elblag, 82-300

  • Centrum Badan Klinicznych PI-House

    Gdansk, 80-546

  • Specjalistyczny Gabinet Diabetologiczny Radoslaw Rumianowski

    Gorzów Wielkopolski, Lubusz Voivodeship, 66-400

  • Uniwersyteckie Centrum Kliniczne im. prof. Gibinskiego, SUM

    Katowice, 40-752

  • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie

    Krakow, 30-688

  • Centrum Terapii Wspolczesnej J.M. Jasnorzewska S.K.A.

    Lodz, 90-338

  • NZOZ Przychodnia Specjalistyczna Medica

    Lublin, Lubelski, 20-538

  • Centrum Zdrowia Metabolicznego

    Poznan, Wielkopolskie Voivodeship, 60-589

  • Gaja Poradnie Lekarskie

    Poznan, 61-251

  • Centrum Medyczne "Diabetika"

    Radom, 26-600

  • NBR Polska Tomasz Klodawski

    Warsaw, 00-710

  • SP CSK Klinika Diabetologii i Chorob Wewnetrznych

    Warsaw, 02-097

  • Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych I Administracji

    Warsaw, 02-507

  • Centrum Medyczne Oporow

    Wroclaw, 52-416

  • Prywatny Gabinet Janusz Gumprecht

    Zabrze, 41-800

Other trials in Poland

Bulgaria17 sites
  • MHAT - Blagoevgrad AD, Department of Internal Diseases

    Blagoevgrad, 2700

  • Medical Center Zdrave Lom EOOD

    Lom, 3600

  • UMHAT Pulmed OOD - Pazardzhik, Department of Internal Diseases

    Pazardzhik, 4400

  • "MHAT - Pazardzhik"

    Pazardzhik, 4401

  • OCSOMCE - Dr. Albena Dinkova EOOD

    Pleven, 5800

  • UMHAT Kaspela EOOD, Endocrinology and Metabolic Diseases Clinic

    Plovdiv, 4001

  • MHAT Sveta Karidad EAD

    Plovdiv, 4004

  • MHAT Hadzhi Dimitar OOD

    Sliven, 8800

  • Medical center Smolyan clinical research OOD

    Smolyan, 4700

  • UMHAT "Aleksandrovska"

    Sofia, 1431

  • USHATE "Akad. Ivan Penchev" Second Clinic of Endocrinology

    Sofia, 1431

  • Medical Institute of Ministry of interior

    Sofia, 1606

  • UMHAT Sveta Marina EAD

    Varna, 9010

  • AIPSMC Dr. Artin Magardichyan EOOD

    Varna, 9020

  • MHAT- Hristo Botev AD

    Vratsa, 3000

  • MHAT- Hristo Botev

    Vratsa, 3001

  • MHAT Sveti Panteleimon - Yambol AD

    Yambol, 8600

Other trials in Bulgaria

Canada15 sites
  • LMC ClinRsrh Inc.Brampton

    Brampton, Ontario, L6S 0C6

  • LMC Clin Res Inc. Calgary

    Calgary, Alberta, T2H 2G4

  • C-endo Diab Endo Clin Calgery

    Calgary, Alberta, T2V 4J2

  • LMC Clinical Res Thornhill

    Concord, Ontario, L4K 4M2

  • LMC Endo Ctr (Etobicoke) Ltd

    Etobicoke, Ontario, M9R 4E1

  • Wharton Med Clin Trials

    Hamilton, Ontario, L8L 5G8

  • G.A. Research Associates Ltd.

    Moncton, New Brunswick, E1G 1A7

  • Applied Med Inf Res

    Montreal, Quebec, H4A 3T2

  • LMC Research Inc. Ottawa

    Nepean, Ontario, K2J 0V2

  • LMC Oakville

    Oakville, Ontario, L6M 1M1

  • LMC Clin Rsrch Inc. (Montreal)

    Saint-Laurent, Quebec, H4T 1Z9

  • Stayner Medical Clinic

    Stayner, Ontario, L0M 1S0

  • Winterberry Family Medicine

    Stoney Creek, Ontario, L8J 0B6

  • LMC Endo Centres Ltd.(Bayview)

    Toronto, Ontario, M4G 3E8

  • Mount Sinai Hospital

    Toronto, Ontario, M5T 3L9

Other trials in Canada

Hungary11 sites
  • Óbudai Egészségügyi Centrum

    Budapest, Pest County, 1036

  • Szőcs Depot Egészségügyi Szolgáltató Kft.

    Budapest, 1042

  • Bajcsy-Zsilinszky Kórház

    Budapest, 1106

  • Dr. Vass László Egészségügyi Intézmény Diab. Szakrendelés

    Budapest, 1152

  • Debreceni Egyetem Klinikai Központ Belgyógyászati Klinika D épület

    Debrecen, 4043

  • Debreceni Egyetem Klinikai Központ Belgyógyászati Klinika

    Debrecen, H-4032

  • Komáromi Selye János Kórház

    Komárom, Komárom-Esztergom, 2900

  • PTE-AOK II. Belgyogyaszati Klinika es Nephrologiai Centrum

    Pécs, Baranya Vármegye, 7623

  • Fejér Megyei Szent György Oktatókórház

    Székesfehérvár, 8000

  • Tolna megyei Balassa János Kórház

    Szekszárd, 7100

  • Vas Vármegyei Markusovszky Egyetemi Oktatókórház

    Szombathely, 9700

Other trials in Hungary

Slovakia10 sites
  • DIADA, s.r.o.

    Bardejov, 08501

  • Diabetologicka ambulancia Diabetes care, s.r.o.

    Hnúšťa, 98101

  • Diabetologicka ambulancia DIAMO s.r.o.

    Kežmarok, 06001

  • MOMED, s.r.o

    Kráľovský Chlmec, 077 01

  • IN-DIA s.r.o.

    Lučenec, 984 01

  • Diabetologicka ambulancia MUDr. Alena Lomencikova, s.r.o

    Martin, 036 01

  • DIABETOL, s.r.o.

    Prešov, 080 01

  • OLIVER - MED s.r.o.

    Rimavská Sobota, 979 01

  • MEDI-DIA s.r.o.

    Sabinov, 08301

  • Diabetologicka ambulancia MUDr. Gabriela Zimova

    Spišská Nová Ves, 052 01

Other trials in Slovakia

Czechia9 sites
  • Ordinace pro choroby srdce

    Chomutov, 430 02

  • Diabetologická a endokrinologická ambulance Hlučín

    Hlučín, 748 01

  • Diahaza s.r.o.

    Holešov, 76901

  • Diahelp - diabetologie

    Pardubice, 530 02

  • DIALINE s.r.o.

    Plzeň 3, 301 00

  • Fakultni nemocnice Kralovske Vinohrady

    Prague, 100 00

  • DiaGolfova spol s.r.o.

    Prague, 102 00

  • Diabet2 s.r.o.

    Prague, 110 00

  • Diabetologická a endokrinologická ambulance Praha

    Prague, 140 21

Other trials in Czechia

Germany8 sites
  • Institut für Klinische Forschung und Entwicklung

    Berlin, 10437

  • Plassmann

    Essen, 45359

  • Zentrum für klinische Forschung, Dr. med. Lüdemann

    Falkensee, 14612

  • Diabetes Zentrum Wandsbek Berufsausuebungsgemeinschaft GbR

    Hamburg, 22041

  • Wendisch/Dahl Hamburg (DZHW)

    Hamburg, 22607

  • Institut für Diabetesforschung GmbH Münster - Dr. med. Rose

    Münster, 48145

  • RED-Institut für medizinische Forschung und Fortbildung GmbH

    Oldenburg in Holstein, 23758

  • Praxis Dr. med. Wenzl-Bauer

    Rehlingen-Siersburg, 66780

Other trials in Germany

Australia7 sites
  • Fremantle Hospital

    Fremantle, Western Australia, 6160

  • Barwon Health (The Geelong Hospital)

    Geelong, Victoria, 3220

  • Royal Brisbane and Women's Hospital

    Herston, Queensland, 4029

  • South Australian Endocrine Research

    Keswick, South Australia, 5035

  • Liverpool Hospital

    Liverpool, New South Wales, 2170

  • Core Research Centre

    Milton, Queensland, 4064

  • Southern Adelaide Diabetes & Endocrine Services

    Oaklands Park, South Australia, 5046

Other trials in Australia

Croatia7 sites
  • Opca bolnica Bjelovar

    Bjelovar, 43000

  • Klinicki bolnicki centar Osijek

    Osijek, 31 000

  • KBC Rijeka, Endokrinologija

    Rijeka, Primorje-Gorski Kotar County, 51 000

  • General Hospital Dr. Josip Bencevic_Diabetic department

    Slavonski Brod, 35 000

  • Poliklinika Solmed

    Zagreb, City of Zagreb, 10000

  • KB Dubrava, Zavod za endokrinologiju i dijabetes

    Zagreb, 10000

  • Klinicka bolnica Sveti Duh

    Zagreb, 10000

Other trials in Croatia

Estonia6 sites
  • Private Endocrnologist Dr Viitas

    Pärnu, 80018

  • East Tallinn Central Hospital

    Tallinn, 10138

  • Merelahe Family Doctors Centre

    Tallinn, 10617

  • Estonian Diabetes Centre

    Tallinn, 13419

  • Tartu University Hospital Internal Medicine Clinic

    Tartu, 50406

  • SA Viljandi Haigla

    Viljandi, 71024

Other trials in Estonia

Slovenia5 sites
  • General Hospital Celje

    Celje, SI-3000

  • Healthcare Centre Koper

    Koper, SI-6000

  • UKC Ljubljana, Endocrinology and Diabetes

    Ljubljana, SI-1000

  • UKC Maribor - diabetes

    Maribor, SI-2000

  • Healthcare Centre Nova Gorica

    Nova Gorica, SI-5000

Other trials in Slovenia

Taiwan2 sites
  • Taichung Veterans General Hospital

    Taichung, 407

  • National Cheng Kung University Hospital

    Tainan, 704

Other trials in Taiwan

Puerto Rico1 site
  • Manati Ctr For Clin Research

    Manati, 00674

Other trials in Puerto Rico

About this study

Official title: Efficacy and Safety of Once-daily Oral Semaglutide 25 mg and 50 mg Compared With 14 mg in Subjects With Type 2 Diabetes

This study compares three doses of once daily semaglutide tablets in people with type 2 diabetes who were previously treated with other oral anti-diabetic medicines. Participants will be initiated on the lowest starting dose of 3 mg and gradually increased until they reach the final trial dose of 14 mg, 25 mg or 50 mg once daily semaglutide tablets. The final three doses will be randomized (i.e., decided by chance). Participants will be administered one tablet per day for 68 weeks. Women cannot take part if they are pregnant, breast-feeding or planning to become pregnant during the study period. Women who can get pregnant will be checked for pregnancy via urine tests. Once daily semaglutide tablets (3 mg, 7 mg and 14 mg) are approved for the treatment of type 2 diabetes in the US, in the EU and in some other countries, under the brand name Rybelsus®.

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

What participants receive

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

  • Oral semaglutideDrug

    Participants will receive once daily semaglutide tablets (oral administration) in a dose escalating manner for 68 weeks.

Study groups in NCT04707469
Study groupRoleWhat they receive
Oral semaglutide 50 mgExperimentalParticipants will receive once daily semaglutide tablets in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8), 14 mg (week 9-12), 25 mg (week 13-16) and 50 mg (week 17-68).
Receives: Drug: Oral semaglutide
Oral semaglutide 25 mgExperimentalParticipants will receive once daily semaglutide tablets in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8), 14 mg (week 9-12) and 25 mg (week 13-68).
Receives: Drug: Oral semaglutide
Oral semaglutide 14 mgActive comparatorParticipants will receive once daily semaglutide tablets in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8) and 14 mg (week 9-68).
Receives: Drug: Oral semaglutide

What is being measured

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

  1. Change From Baseline in Glycated Haemoglobin (HbA1c) (Week 52)

    Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment. Percentage point refers to arithmetic difference between two percentages.

    Measured: Baseline (week 0), week 52

Secondary outcomes (38)
  1. Change From Baseline in Body Weight (Week 52)

    Change from baseline (week 0) in body weight was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline (week 0), week 52

  2. Change From Baseline in HbA1c (Week 68)

    Change from baseline (week 0) in HbA1c was evaluated at week 68. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment. Percentage point refers to arithmetic difference between two percentages.

    Measured: Baseline (week 0), week 68

  3. Change From Week 12 in HbA1c (Week 52)

    Change in HbA1c was evaluated from week 12 to week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment. Percentage point refers to arithmetic difference between two percentages.

    Measured: Week 12, Week 52

  4. Change From Baseline in Fasting Plasma Glucose (FPG) (Week 52)

    Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline (week 0), week 52

  5. Change From Baseline in FPG (Week 68)

    Change from baseline (week 0) in FPG was evaluated at week 68. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline (week 0), week 68

  6. Percentage of Participants Who Achieved HbA1c Less Than (<) 7.0 (Percent [%]) (Week 52)

    Percentage of participants who achieved HbA1c <7.0 % at week 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: At week 52

  7. Percentage of Participants Who Achieved HbA1c < 7.0 % (Week 68)

    Percentage of participants who achieved HbA1c <7.0 % at week 68 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: At week 68

  8. Percentage of Participants Who Achieved HbA1c Less Than or Equal to (<=) 6.5 % (Week 52)

    Percentage of participants who achieved HbA1c <=6.5 % at week 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: At week 52

  9. Percentage of Participants Who Achieved HbA1c <= 6.5 % (Week 68)

    Percentage of participants who achieved HbA1c <=6.5 % at week 68 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: At week 68

  10. Time to Event Analyses of Rescue Medication

    Time to event analyses of rescue medication was evaluated from baseline (week 0) to week 68. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline (week 0), week 68

  11. Change From Baseline in Body Weight (Week 68)

    Change from baseline (week 0) in body weight was evaluated at week 68. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline (week 0), week 68

  12. Percentage Change From Baseline in Body Weight (Week 52)

    Percentage change from baseline (week 0) in body weight was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline (week 0), week 52

  13. Percentage Change From Baseline in Body Weight (Week 68)

    Percentage change from baseline (week 0) in body weight was evaluated at week 68. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline (week 0), week 68

  14. Percentage Change From Week 12 in Body Weight (Week 52)

    Percentage change in body weight was evaluated from week 12 to week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Week 12, Week 52

  15. Change From Baseline in Body Mass Index (BMI) (Week 52)

    Change from baseline (week 0) in body mass index (BMI) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline (week 0), week 52

  16. Change From Baseline in BMI (Week 68)

    Change from baseline (week 0) in BMI was evaluated at week 68. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline (week 0), week 68

  17. Change From Baseline in Waist Circumference (Week 52)

    Change from baseline (week 0) in waist circumference was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline (week 0), week 52

  18. Change From Baseline in Waist Circumference (Week 68)

    Change from baseline (week 0) in waist circumference was evaluated at week 68. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline (week 0), week 68

  19. Percentage of Participants Who Achieved Weight Loss Greater Than or Equal to (>=) 5 % (Week 52)

    Percentage of participants who achieved weight loss >= 5 % at week 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: At week 52

  20. Percentage of Participants Who Achieved Weight Loss >= 5 % (Week 68)

    Percentage of participants who achieved weight loss >= 5 % at week 68 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: At week 68

  21. Percentage of Participants Who Achieved Weight Loss >= 10 % (Week 52)

    Percentage of participants who achieved weight loss >= 10 % at week 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: At week 52

  22. Percentage of Participants Who Achieved Weight Loss >= 10 % (Week 68)

    Percentage of participants who achieved weight loss >= 10 % at week 68 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: At week 68

  23. Change From Baseline in Total Cholesterol (Week 52)

    Change from baseline (week 0) in total cholesterol was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline, Week 52

  24. Change From Baseline in Total Cholesterol (Week 68)

    Change from baseline (week 0) in total cholesterol was evaluated at week 68. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline, Week 68

  25. Change From Baseline in Low Density Lipoproteins (LDL) (Week 52)

    Change from baseline (week 0) in LDL was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline, Week 52

  26. Change From Baseline in LDL (Week 68)

    Change from baseline (week 0) in LDL was evaluated at week 68. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline, Week 68

  27. Change From Baseline in High Density Lipoproteins (HDL) (Week 52)

    Change from baseline (week 0) in HDL was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline, Week 52

  28. Change From Baseline in HDL (Week 68)

    Change from baseline (week 0) in HDL was evaluated at week 68. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline, Week 68

  29. Change From Baseline in Triglycerides (Week 52)

    Change from baseline (week 0) in triglycerides was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline, Week 52

  30. Change From Baseline in Triglycerides (Week 68)

    Change from baseline (week 0) in triglycerides was evaluated at week 68. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

    Measured: Baseline, Week 68

  31. Number of Adverse Events

    An adverse event (AE) defined as any unfavourable and unintended sign, including an abnormal laboratory finding, symptom or disease (new or exacerbated) temporally associated with the use of an investigational medicinal products (IMP). Results are based on the data from the on-treatment observation period, which was the time period when a participant was on trial treatment, including any period after initiation of rescue medication.

    Measured: From baseline (week 0) up to week 73

  32. Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 Milligram Per Decilitre [mg/dL]) or Severe Hypoglycaemic Episodes (Level 3)

    Hypoglycaemic episodes were classified according to the American Diabetes Association 2018/ International Hypoglycaemia Study Group 2017, where glycemic criteria for level 2 was < 3.0 mmol/L (54 mg/dL) and level 3 had no specific glucose threshold. Results are based on the data from the on-treatment observation period, which was the time period when a participant was on trial treatment, including any period after initiation of rescue medication.

    Measured: From baseline (week 0) up to week 68

  33. Change From Baseline in Systolic Blood Pressure (Week 52)

    Change from baseline (week 0) in systolic blood pressure at week 52 are presented. Results are based on the data from the on-treatment observation period, which was the time period when a participant was on trial treatment, including any period after initiation of rescue medication.

    Measured: Baseline (week 0), week 52

  34. Change From Baseline in Systolic Blood Pressure (Week 68)

    Change from baseline (week 0) in systolic blood pressure at week 68 are presented. Results are based on the data from the on-treatment observation period, which was the time period when a participant was on trial treatment, including any period after initiation of rescue medication.

    Measured: Baseline (week 0), week 68

  35. Change From Baseline in Diastolic Blood Pressure (Week 52)

    Change from baseline (week 0) in diastolic blood pressure at week 52 are presented. Results are based on the data from the on-treatment observation period, which was the time period when a participant was on trial treatment, including any period after initiation of rescue medication.

    Measured: Baseline (week 0), week 52

  36. Change From Baseline in Diastolic Blood Pressure (Week 68)

    Change from baseline (week 0) in diastolic blood pressure at week 68 are presented. Results are based on the data from the on-treatment observation period, which was the time period when a participant was on trial treatment, including any period after initiation of rescue medication.

    Measured: Baseline (week 0), week 68

  37. Change From Baseline in Pulse (Week 52)

    Change from baseline (week 0) in pulse at week 52 are presented. Results are based on the data from the on-treatment observation period, which was the time period when a participant was on trial treatment, including any period after initiation of rescue medication.

    Measured: Baseline (week 0), week 52

  38. Change From Baseline in Pulse (Week 68)

    Change from baseline (week 0) in pulse at week 68 are presented. Results are based on the data from the on-treatment observation period, which was the time period when a participant was on trial treatment, including any period after initiation of rescue medication.

    Measured: Baseline (week 0), week 68

Timeline

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

  1. First posted13 Jan 2021
  2. Study start15 Jan 2021
  3. Primary completion7 Mar 2023
  4. Study completion8 Mar 2023

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
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,606 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04707469
Sponsor's protocol ID
NN9924-4635
Other IDs
U1111-1247-0210, 2020-000299-39
Acronym
PIONEER PLUS
Status last verified
Nov 2025
First submitted
12 Jan 2021
Last updated
9 Dec 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Publications

  • Aroda VR, Aberle J, Bardtrum L, Christiansen E, Knop FK, Gabery S, Pedersen SD, Buse JB. Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial. Lancet. 2023 Aug 26;402(10403):693-704. doi: 10.1016/S0140-6736(23)01127-3. Epub 2023 Jun 26.

    PubMed 37385279

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Oral semaglutide in people with Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 228 sites in 15 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 11 inclusion and 3 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 9 Dec 2025. 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, Poland, Bulgaria, Canada and 10 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. 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 3 Apr 2024). 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?

Change From Baseline in Glycated Haemoglobin (HbA1c) (Week 52) (time frame: Baseline (week 0), week 52). 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 NCT04707469, which also lists 1 linked publication.

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 9 Dec 2025.

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