Efficacy and Safety of Oral Semaglutide Versus Liraglutide and Versus Placebo in Subjects With Type 2 Diabetes Mellitus

NCT ID: NCT02863419

Last Updated: 2022-07-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

711 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-08-10

Study Completion Date

2018-03-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This trial is conducted globally. The aim of this trial is to investigate efficacy and safety of oral Semaglutide versus Liraglutide and versus Placebo in Subjects with Type 2 Diabetes Mellitus.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Diabetes Diabetes Mellitus, Type 2

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Oral Semaglutide

Group Type EXPERIMENTAL

semaglutide

Intervention Type DRUG

Oral semaglutide once-daily.

Liraglutide

Group Type ACTIVE_COMPARATOR

liraglutide

Intervention Type DRUG

Subcutaneous (s.c.) injection once-daily.

Placebo

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Placebo once-daily.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

semaglutide

Oral semaglutide once-daily.

Intervention Type DRUG

liraglutide

Subcutaneous (s.c.) injection once-daily.

Intervention Type DRUG

placebo

Placebo once-daily.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
* Male or female, age above or equal to 18 years at the time of signing informed consent. For Japan only: Male or female, age at least 20 years at the time of signing informed consent
* Diagnosed with type 2 diabetes mellitus for at least 90 days prior to day of screening.
* HbA1c (glycosylated haemoglobin) of 7.0-9.5 % (53-80.3 mmol/mol) (both inclusive)
* Stable daily dose of metformin (above or equal to 1500 mg or maximum tolerated dose as documented in the subject medical record) alone or in combination with a stable daily dose of a SGLT-2 (sodium-glucose co-transporter-2) inhibitor for at least 90 days prior to day of screening (fixed-dose combinations are allowed)

* Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation
* History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ)
* History of diabetic ketoacidosis

Exclusion Criteria

* Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice).For certain specific countries: Additional specific requirements apply
* Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol
* 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 and potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)
* Any of the following: myocardial infarction (MI), stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening
* Subjects presently classified as being in New York Heart Association (NYHA) Class IV
* Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
* Subjects with ALT (alanine aminotransferase) above 2.5 × upper normal limit (UNL)
* Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) below 60 mL/min/1.73 m\^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Novo Nordisk A/S

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Global Clinical Registry (GCR, 1452)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Novo Nordisk Investigational Site

Birmingham, Alabama, United States

Site Status

Novo Nordisk Investigational Site

Los Alamitos, California, United States

Site Status

Novo Nordisk Investigational Site

San Diego, California, United States

Site Status

Novo Nordisk Investigational Site

Denver, Colorado, United States

Site Status

Novo Nordisk Investigational Site

Hallandale, Florida, United States

Site Status

Novo Nordisk Investigational Site

Jacksonville, Florida, United States

Site Status

Novo Nordisk Investigational Site

Miami, Florida, United States

Site Status

Novo Nordisk Investigational Site

Ocala, Florida, United States

Site Status

Novo Nordisk Investigational Site

Orlando, Florida, United States

Site Status

Novo Nordisk Investigational Site

Orlando, Florida, United States

Site Status

Novo Nordisk Investigational Site

Ormond Beach, Florida, United States

Site Status

Novo Nordisk Investigational Site

St. Petersburg, Florida, United States

Site Status

Novo Nordisk Investigational Site

West Palm Beach, Florida, United States

Site Status

Novo Nordisk Investigational Site

Peoria, Illinois, United States

Site Status

Novo Nordisk Investigational Site

Topeka, Kansas, United States

Site Status

Novo Nordisk Investigational Site

Slidell, Louisiana, United States

Site Status

Novo Nordisk Investigational Site

Butte, Montana, United States

Site Status

Novo Nordisk Investigational Site

Lebanon, New Hampshire, United States

Site Status

Novo Nordisk Investigational Site

Teaneck, New Jersey, United States

Site Status

Novo Nordisk Investigational Site

Albany, New York, United States

Site Status

Novo Nordisk Investigational Site

Mineola, New York, United States

Site Status

Novo Nordisk Investigational Site

Greensboro, North Carolina, United States

Site Status

Novo Nordisk Investigational Site

Morganton, North Carolina, United States

Site Status

Novo Nordisk Investigational Site

Wilmington, North Carolina, United States

Site Status

Novo Nordisk Investigational Site

Dublin, Ohio, United States

Site Status

Novo Nordisk Investigational Site

Maumee, Ohio, United States

Site Status

Novo Nordisk Investigational Site

Norman, Oklahoma, United States

Site Status

Novo Nordisk Investigational Site

McMurray, Pennsylvania, United States

Site Status

Novo Nordisk Investigational Site

Summerville, South Carolina, United States

Site Status

Novo Nordisk Investigational Site

Bristol, Tennessee, United States

Site Status

Novo Nordisk Investigational Site

Arlington, Texas, United States

Site Status

Novo Nordisk Investigational Site

Dallas, Texas, United States

Site Status

Novo Nordisk Investigational Site

Dallas, Texas, United States

Site Status

Novo Nordisk Investigational Site

Houston, Texas, United States

Site Status

Novo Nordisk Investigational Site

North Richland Hills, Texas, United States

Site Status

Novo Nordisk Investigational Site

San Antonio, Texas, United States

Site Status

Novo Nordisk Investigational Site

San Antonio, Texas, United States

Site Status

Novo Nordisk Investigational Site

Newport News, Virginia, United States

Site Status

Novo Nordisk Investigational Site

Richmond, Virginia, United States

Site Status

Novo Nordisk Investigational Site

Virginia Beach, Virginia, United States

Site Status

Novo Nordisk Investigational Site

Karlovac, , Croatia

Site Status

Novo Nordisk Investigational Site

Osijek, , Croatia

Site Status

Novo Nordisk Investigational Site

Slavonski Brod, , Croatia

Site Status

Novo Nordisk Investigational Site

Zagreb, , Croatia

Site Status

Novo Nordisk Investigational Site

Zagreb, , Croatia

Site Status

Novo Nordisk Investigational Site

Náchod, , Czechia

Site Status

Novo Nordisk Investigational Site

Pilsen, , Czechia

Site Status

Novo Nordisk Investigational Site

Prague, , Czechia

Site Status

Novo Nordisk Investigational Site

Bochum, , Germany

Site Status

Novo Nordisk Investigational Site

Duisburg, , Germany

Site Status

Novo Nordisk Investigational Site

Falkensee, , Germany

Site Status

Novo Nordisk Investigational Site

Hamburg, , Germany

Site Status

Novo Nordisk Investigational Site

Ludwigshafen, , Germany

Site Status

Novo Nordisk Investigational Site

Oldenburg I. Holst, , Germany

Site Status

Novo Nordisk Investigational Site

Saint Ingbert-Oberwürzbach, , Germany

Site Status

Novo Nordisk Investigational Site

Villingen-Schwenningen, , Germany

Site Status

Novo Nordisk Investigational Site

Budapest, , Hungary

Site Status

Novo Nordisk Investigational Site

Budapest, , Hungary

Site Status

Novo Nordisk Investigational Site

Gyula, , Hungary

Site Status

Novo Nordisk Investigational Site

Kalocsa, , Hungary

Site Status

Novo Nordisk Investigational Site

Nagykanizsa, , Hungary

Site Status

Novo Nordisk Investigational Site

Szeged, , Hungary

Site Status

Novo Nordisk Investigational Site

Székesfehérvár, , Hungary

Site Status

Novo Nordisk Investigational Site

Szigetvár, , Hungary

Site Status

Novo Nordisk Investigational Site

Szolnok, , Hungary

Site Status

Novo Nordisk Investigational Site

Tatabánya, , Hungary

Site Status

Novo Nordisk Investigational Site

Bunkyo-ku, Tokyo, , Japan

Site Status

Novo Nordisk Investigational Site

Kumamoto-shi,Kumamoto, , Japan

Site Status

Novo Nordisk Investigational Site

Mito-shi, Ibaraki, , Japan

Site Status

Novo Nordisk Investigational Site

Okawa-shi, Fukuoka, , Japan

Site Status

Novo Nordisk Investigational Site

Sapporo-shi, Hokkaido, , Japan

Site Status

Novo Nordisk Investigational Site

Shimotsuke-shi, Tochigi, , Japan

Site Status

Novo Nordisk Investigational Site

Suita-shi, Osaka, , Japan

Site Status

Novo Nordisk Investigational Site

Tochigi, , Japan

Site Status

Novo Nordisk Investigational Site

Yamato-shi, Kanagawa, , Japan

Site Status

Novo Nordisk Investigational Site

Ogre, , Latvia

Site Status

Novo Nordisk Investigational Site

Riga, , Latvia

Site Status

Novo Nordisk Investigational Site

Riga, , Latvia

Site Status

Novo Nordisk Investigational Site

Riga, , Latvia

Site Status

Novo Nordisk Investigational Site

Bialystok, , Poland

Site Status

Novo Nordisk Investigational Site

Bydgoszcz, , Poland

Site Status

Novo Nordisk Investigational Site

Gdansk, , Poland

Site Status

Novo Nordisk Investigational Site

Gniewkowo, , Poland

Site Status

Novo Nordisk Investigational Site

Krakow, , Poland

Site Status

Novo Nordisk Investigational Site

Poznan, , Poland

Site Status

Novo Nordisk Investigational Site

Szczecin, , Poland

Site Status

Novo Nordisk Investigational Site

Warsaw, , Poland

Site Status

Novo Nordisk Investigational Site

Wroclaw, , Poland

Site Status

Novo Nordisk Investigational Site

Toa Baja, , Puerto Rico

Site Status

Novo Nordisk Investigational Site

Bardejov, , Slovakia

Site Status

Novo Nordisk Investigational Site

Bratislava, , Slovakia

Site Status

Novo Nordisk Investigational Site

Košice, , Slovakia

Site Status

Novo Nordisk Investigational Site

Nitra, , Slovakia

Site Status

Novo Nordisk Investigational Site

Rožňava, , Slovakia

Site Status

Novo Nordisk Investigational Site

Vrútky, , Slovakia

Site Status

Novo Nordisk Investigational Site

Benoni, Gauteng, South Africa

Site Status

Novo Nordisk Investigational Site

Johannesburg, Gauteng, South Africa

Site Status

Novo Nordisk Investigational Site

Durban, KwaZulu-Natal, South Africa

Site Status

Novo Nordisk Investigational Site

Durban, KwaZulu-Natal, South Africa

Site Status

Novo Nordisk Investigational Site

Cape Town, Western Cape, South Africa

Site Status

Novo Nordisk Investigational Site

Kyiv, , Ukraine

Site Status

Novo Nordisk Investigational Site

Odesa, , Ukraine

Site Status

Novo Nordisk Investigational Site

Vinnytsia, , Ukraine

Site Status

Novo Nordisk Investigational Site

Ajman, , United Arab Emirates

Site Status

Novo Nordisk Investigational Site

Al Mafraq, , United Arab Emirates

Site Status

Novo Nordisk Investigational Site

Dubai, , United Arab Emirates

Site Status

Novo Nordisk Investigational Site

Rahba City, , United Arab Emirates

Site Status

Novo Nordisk Investigational Site

Umm Al Quwain City, , United Arab Emirates

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Croatia Czechia Germany Hungary Japan Latvia Poland Puerto Rico Slovakia South Africa Ukraine United Arab Emirates

References

Explore related publications, articles, or registry entries linked to this study.

Pratley R, Amod A, Hoff ST, Kadowaki T, Lingvay I, Nauck M, Pedersen KB, Saugstrup T, Meier JJ; PIONEER 4 investigators. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. Lancet. 2019 Jul 6;394(10192):39-50. doi: 10.1016/S0140-6736(19)31271-1. Epub 2019 Jun 8.

Reference Type RESULT
PMID: 31186120 (View on PubMed)

Araki E, Terauchi Y, Watada H, Deenadayalan S, Christiansen E, Horio H, Kadowaki T. Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A post hoc subgroup analysis of the PIONEER 1, 3, 4 and 8 trials. Diabetes Obes Metab. 2021 Dec;23(12):2785-2794. doi: 10.1111/dom.14536. Epub 2021 Sep 27.

Reference Type RESULT
PMID: 34472698 (View on PubMed)

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.

Reference Type RESULT
PMID: 35373893 (View on PubMed)

Ren H, Berry S, Malkin SJP, Hunt B, Bain S. Early use of oral semaglutide in the UK: A cost-effectiveness analysis versus continuing metformin and SGLT-2 inhibitor therapy. BMJ Open. 2023 Sep 29;13(9):e070473. doi: 10.1136/bmjopen-2022-070473.

Reference Type DERIVED
PMID: 37775297 (View on PubMed)

Pratley RE, Crowley MJ, Gislum M, Hertz CL, Jensen TB, Khunti K, Mosenzon O, Buse JB. Oral Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses. Diabetes Ther. 2021 Apr;12(4):1099-1116. doi: 10.1007/s13300-020-00994-9. Epub 2021 Mar 4.

Reference Type DERIVED
PMID: 33660198 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32267058 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31903692 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

http://novonordisk-trials.com

Clinical Trials at Novo Nordisk

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2015-005210-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1176-6029

Identifier Type: OTHER

Identifier Source: secondary_id

NN9924-4224

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.