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

NCT ID: NCT04707469

Last Updated: 2025-12-09

Study Results

Results available

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

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1606 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-15

Study Completion Date

2023-03-08

Brief Summary

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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®.

Detailed Description

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Conditions

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Diabetes Mellitus, Type 2

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Sponsor staff involved in the clinical trial is masked according to company standard procedures.

Study Groups

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Oral semaglutide 50 mg

Participants 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).

Group Type EXPERIMENTAL

Oral semaglutide

Intervention Type DRUG

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

Oral semaglutide 25 mg

Participants 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).

Group Type EXPERIMENTAL

Oral semaglutide

Intervention Type DRUG

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

Oral semaglutide 14 mg

Participants 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).

Group Type ACTIVE_COMPARATOR

Oral semaglutide

Intervention Type DRUG

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

Interventions

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Oral semaglutide

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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 \*:

* 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).

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novo Nordisk A/S

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Transparency (dept. 1452)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

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American Clinical Trials

Buena Park, California, United States

Site Status

Valley Research

Fresno, California, United States

Site Status

Velocity Clin Res San Diego

La Mesa, California, United States

Site Status

First Valley Medical Group

Lancaster, California, United States

Site Status

Pacific Clinical Studies

Los Alamitos, California, United States

Site Status

Velocity Clin Res Los Angeles

Los Angeles, California, United States

Site Status

Diabetes Medical Center Of California

Northridge, California, United States

Site Status

Desert Oasis Hlthcr Med Group

Palm Springs, California, United States

Site Status

Gateway Research Center

Poway, California, United States

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Encompass Clinical Research_Spring Valley

Spring Valley, California, United States

Site Status

Diablo Clinical Research, Inc.

Walnut Creek, California, United States

Site Status

San Fernando Valley Hlth Inst, LLC

West Hills, California, United States

Site Status

University of Colorado Hospital

Aurora, Colorado, United States

Site Status

Optumcare Clinical Trials,LLC-Golden

Colorado Springs, Colorado, United States

Site Status

Chase Medical Research LLC

Waterbury, Connecticut, United States

Site Status

Alliance for Multispec Res

Coral Gables, Florida, United States

Site Status

Northeast Research Institute

Jacksonville, Florida, United States

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San Marcus Res Clin Miami Lakes

Miami Lakes, Florida, United States

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Complete Health Research

Ormond Beach, Florida, United States

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Clinical Trial Res Assoc,Inc

Plantation, Florida, United States

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Progressive Medical Research

Port Orange, Florida, United States

Site Status

Endo Res Solutions Inc

Roswell, Georgia, United States

Site Status

East West Med Res Inst

Honolulu, Hawaii, United States

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Elite Clinical Trials

Blackfoot, Idaho, United States

Site Status

Rocky Mt Clin Res, LLC

Idaho Falls, Idaho, United States

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Solaris Clinical Research

Meridian, Idaho, United States

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Cedar-Crosse Research Center

Chicago, Illinois, United States

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Macoupin Research Group

Gillespie, Illinois, United States

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UnityPoint Health-Diabetes Care Center

Peoria, Illinois, United States

Site Status

Evanston Premier Hlthcr Res

Skokie, Illinois, United States

Site Status

Midwest Inst For Clin Res

Indianapolis, Indiana, United States

Site Status

Iowa Diab & Endo Res Center

West Des Moines, Iowa, United States

Site Status

Cotton O'Neil Diab & Endo Ctr

Topeka, Kansas, United States

Site Status

The Research Group of Lexington LLC

Lexington, Kentucky, United States

Site Status

L-MARC Research Center

Louisville, Kentucky, United States

Site Status

Pennington Biom Res Ctr

Baton Rouge, Louisiana, United States

Site Status

Centex Studies, Inc._Lake Charles

Lake Charles, Louisiana, United States

Site Status

MD Medical Research

Oxon Hill, Maryland, United States

Site Status

Brigham & Women's Hospital

Boston, Massachusetts, United States

Site Status

MassResearch, LLC

Waltham, Massachusetts, United States

Site Status

Aa Mrc Llc

Flint, Michigan, United States

Site Status

Arcturus Healthcare, PLC.

Troy, Michigan, United States

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Mercury Str Med Grp, PLLC

Butte, Montana, United States

Site Status

Univ of Nebraska Medical CTR

Omaha, Nebraska, United States

Site Status

University of Nebraska Medical Center-Diabetes Center

Omaha, Nebraska, United States

Site Status

Premier Research Inc.

Trenton, New Jersey, United States

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UNC Diabetes Care Center_Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

PharmQuest Life Sciences LLC

Greensboro, North Carolina, United States

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Accellacare

Wilmington, North Carolina, United States

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Lillestol Research LLC

Fargo, North Dakota, United States

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Rapid Medical Research Inc

Cleveland, Ohio, United States

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Prestige Clinical Research

Franklin, Ohio, United States

Site Status

Albert J Weisbrot

Mason, Ohio, United States

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Intend Research

Norman, Oklahoma, United States

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Corvallis Clinic PC Clinical Research Department

Corvallis, Oregon, United States

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Preferred Primary Care Physicians_Pittsburgh

Pittsburgh, Pennsylvania, United States

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Palmetto Clinical Research

Greenville, South Carolina, United States

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Palmetto Clinical Research

Summerville, South Carolina, United States

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Holston Medical Group Pc

Bristol, Tennessee, United States

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Chattanooga Medical Research, LLC

Chattanooga, Tennessee, United States

Site Status

Murphy Research Center

Humboldt, Tennessee, United States

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Clinical Neuroscience Solutions

Memphis, Tennessee, United States

Site Status

Arlington Family Res. Ctr Inc

Arlington, Texas, United States

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Velocity Clinical Res-Dallas

Dallas, Texas, United States

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Velocity Clinical Research, Dallas

Dallas, Texas, United States

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UT Southwestern Med Cntr

Dallas, Texas, United States

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Care United Research, LLC

Forney, Texas, United States

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JCCT- Juno NW Houston

Houston, Texas, United States

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JCCT- Juno NW Houston

Houston, Texas, United States

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Southwest Clinical Trials

Houston, Texas, United States

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Family Practice Care Associates

Humble, Texas, United States

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Research Trials Worldwide LLC

Humble, Texas, United States

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Juno Research, LLC_Cary

Katy, Texas, United States

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DCOL Ctr for Clin Res

Longview, Texas, United States

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Research Institute Of Dallas

Plano, Texas, United States

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VIP Trials

San Antonio, Texas, United States

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VIP Trials

San Antonio, Texas, United States

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Consano Clinical Research, LLC

Shavano Park, Texas, United States

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Simcare Medical Research, LLC

Sugar Land, Texas, United States

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Health Res of Hampton Roads

Newport News, Virginia, United States

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York Clinical Research LLC

Norfolk, Virginia, United States

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Dominion Medical Associates

Richmond, Virginia, United States

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Capital Clin Res Ctr,LLC

Olympia, Washington, United States

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Wenatchee Valley Hospital and Clinics

Wenatchee, Washington, United States

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Liverpool Hospital

Liverpool, New South Wales, Australia

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Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

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Core Research Centre

Milton, Queensland, Australia

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South Australian Endocrine Research

Keswick, South Australia, Australia

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Southern Adelaide Diabetes & Endocrine Services

Oaklands Park, South Australia, Australia

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Barwon Health (The Geelong Hospital)

Geelong, Victoria, Australia

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Fremantle Hospital

Fremantle, Western Australia, Australia

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MHAT - Blagoevgrad AD, Department of Internal Diseases

Blagoevgrad, , Bulgaria

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Medical Center Zdrave Lom EOOD

Lom, , Bulgaria

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UMHAT Pulmed OOD - Pazardzhik, Department of Internal Diseases

Pazardzhik, , Bulgaria

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"MHAT - Pazardzhik"

Pazardzhik, , Bulgaria

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OCSOMCE - Dr. Albena Dinkova EOOD

Pleven, , Bulgaria

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UMHAT Kaspela EOOD, Endocrinology and Metabolic Diseases Clinic

Plovdiv, , Bulgaria

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MHAT Sveta Karidad EAD

Plovdiv, , Bulgaria

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MHAT Hadzhi Dimitar OOD

Sliven, , Bulgaria

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Medical center Smolyan clinical research OOD

Smolyan, , Bulgaria

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UMHAT "Aleksandrovska"

Sofia, , Bulgaria

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USHATE "Akad. Ivan Penchev" Second Clinic of Endocrinology

Sofia, , Bulgaria

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Medical Institute of Ministry of interior

Sofia, , Bulgaria

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UMHAT Sveta Marina EAD

Varna, , Bulgaria

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AIPSMC Dr. Artin Magardichyan EOOD

Varna, , Bulgaria

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MHAT- Hristo Botev AD

Vratsa, , Bulgaria

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MHAT- Hristo Botev

Vratsa, , Bulgaria

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MHAT Sveti Panteleimon - Yambol AD

Yambol, , Bulgaria

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LMC Clin Res Inc. Calgary

Calgary, Alberta, Canada

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C-endo Diab Endo Clin Calgery

Calgary, Alberta, Canada

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G.A. Research Associates Ltd.

Moncton, New Brunswick, Canada

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LMC ClinRsrh Inc.Brampton

Brampton, Ontario, Canada

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LMC Clinical Res Thornhill

Concord, Ontario, Canada

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LMC Endo Ctr (Etobicoke) Ltd

Etobicoke, Ontario, Canada

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Wharton Med Clin Trials

Hamilton, Ontario, Canada

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LMC Research Inc. Ottawa

Nepean, Ontario, Canada

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LMC Oakville

Oakville, Ontario, Canada

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Stayner Medical Clinic

Stayner, Ontario, Canada

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Winterberry Family Medicine

Stoney Creek, Ontario, Canada

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LMC Endo Centres Ltd.(Bayview)

Toronto, Ontario, Canada

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Mount Sinai Hospital

Toronto, Ontario, Canada

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Applied Med Inf Res

Montreal, Quebec, Canada

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LMC Clin Rsrch Inc. (Montreal)

Saint-Laurent, Quebec, Canada

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Poliklinika Solmed

Zagreb, City of Zagreb, Croatia

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KBC Rijeka, Endokrinologija

Rijeka, Primorje-Gorski Kotar County, Croatia

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Opca bolnica Bjelovar

Bjelovar, , Croatia

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Klinicki bolnicki centar Osijek

Osijek, , Croatia

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General Hospital Dr. Josip Bencevic_Diabetic department

Slavonski Brod, , Croatia

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KB Dubrava, Zavod za endokrinologiju i dijabetes

Zagreb, , Croatia

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Klinicka bolnica Sveti Duh

Zagreb, , Croatia

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Ordinace pro choroby srdce

Chomutov, , Czechia

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Diabetologická a endokrinologická ambulance Hlučín

Hlučín, , Czechia

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Diahaza s.r.o.

Holešov, , Czechia

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Diahelp - diabetologie

Pardubice, , Czechia

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DIALINE s.r.o.

Plzeň 3, , Czechia

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Fakultni nemocnice Kralovske Vinohrady

Prague, , Czechia

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DiaGolfova spol s.r.o.

Prague, , Czechia

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Diabet2 s.r.o.

Prague, , Czechia

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Diabetologická a endokrinologická ambulance Praha

Prague, , Czechia

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Private Endocrnologist Dr Viitas

Pärnu, , Estonia

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East Tallinn Central Hospital

Tallinn, , Estonia

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Merelahe Family Doctors Centre

Tallinn, , Estonia

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Estonian Diabetes Centre

Tallinn, , Estonia

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Tartu University Hospital Internal Medicine Clinic

Tartu, , Estonia

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SA Viljandi Haigla

Viljandi, , Estonia

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Institut für Klinische Forschung und Entwicklung

Berlin, , Germany

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Plassmann

Essen, , Germany

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Zentrum für klinische Forschung, Dr. med. Lüdemann

Falkensee, , Germany

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Diabetes Zentrum Wandsbek Berufsausuebungsgemeinschaft GbR

Hamburg, , Germany

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Wendisch/Dahl Hamburg (DZHW)

Hamburg, , Germany

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Institut für Diabetesforschung GmbH Münster - Dr. med. Rose

Münster, , Germany

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RED-Institut für medizinische Forschung und Fortbildung GmbH

Oldenburg in Holstein, , Germany

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Praxis Dr. med. Wenzl-Bauer

Rehlingen-Siersburg, , Germany

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PTE-AOK II. Belgyogyaszati Klinika es Nephrologiai Centrum

Pécs, Baranya Vármegye, Hungary

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Komáromi Selye János Kórház

Komárom, Komárom-Esztergom, Hungary

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Óbudai Egészségügyi Centrum

Budapest, Pest County, Hungary

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Szőcs Depot Egészségügyi Szolgáltató Kft.

Budapest, , Hungary

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Bajcsy-Zsilinszky Kórház

Budapest, , Hungary

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Dr. Vass László Egészségügyi Intézmény Diab. Szakrendelés

Budapest, , Hungary

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Debreceni Egyetem Klinikai Központ Belgyógyászati Klinika D épület

Debrecen, , Hungary

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Debreceni Egyetem Klinikai Központ Belgyógyászati Klinika

Debrecen, , Hungary

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Tolna megyei Balassa János Kórház

Szekszárd, , Hungary

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Fejér Megyei Szent György Oktatókórház

Székesfehérvár, , Hungary

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Vas Vármegyei Markusovszky Egyetemi Oktatókórház

Szombathely, , Hungary

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Endolife Specialty Hospitals

Guntur, Andhra Pradesh, India

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Care Outpatient Centre

Hyderabad, Andhra Pradesh, India

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Kurnool Medical Collage

Kurnool, Andhra Pradesh, India

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Nirmal Hospital Pvt. Ltd.

Surat, Gujarat, India

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PGIMS Rohtak

Rohtak, Haryana, India

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Ramaiah Memorial Hospital

Bangalore, Karnataka, India

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Belgaum Diabetes Centre

Belagavi, Karnataka, India

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KLES & Prabhakar Kore Hospital and Research Centre

Belagavi, Karnatka, India

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Amrita Institute Of Medical Sciences & Research Centre

Kochi, Kerala, India

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Seth GS medical college and KEM Hospital

Mumbai, Maharashtra, India

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Apollo Hospital, Navi Mumbai

Mumbai, Maharashtra, India

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Deenanath Mangeshkar Hospital & Research Centre

Pune, Maharashtra, India

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Deenanath Mangeshkar Hospital and Research Centre

Pune, Maharashtra, India

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Inamdar Multispeciality Hospital

Pune, Maharashtra, India

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Fortis Hospital, Shalimar Bagh, New Delhi

New Delhi, National Capital Territory of Delhi, India

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Apollo Hospital

Delhi, New Delhi, India

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All India Institute of Medical Sciences

New Dehli, New Delhi, India

Site Status

Dayanand Medical College & Hospital

Ludhiana, Punjab, India

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Christian Medical College Hospital, Vellore

Vellore, Tamil Nadu, India

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Gandhi Hospital & Medical college

Hyderabad, Telangana, India

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Gleneagles Hospitals

Hyderabad, Telangana, India

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Osmania General Hospital

Hyderabad, Telangana, India

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MV Hospital and Research Centre

Lucknow, Uttar Pradesh, India

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I.P.G.M.E & R Hospital

Kolkata, West Bengal, India

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Apollo Multispeciality Hospital, Kolkata

Kolkata, West Bengal, India

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NZOZ Przychodnia Specjalistyczna Medica

Lublin, Lubelski, Poland

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Specjalistyczny Gabinet Diabetologiczny Radoslaw Rumianowski

Gorzów Wielkopolski, Lubusz Voivodeship, Poland

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Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, Podlaskie Voivodeship, Poland

Site Status

NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny Małgorzata Arciszewska

Bialystok, Podlaskie Voivodeship, Poland

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Kresmed Sp. z o. o.

Bialystok, Podlaskie Voivodeship, Poland

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Centrum Zdrowia Metabolicznego

Poznan, Wielkopolskie Voivodeship, Poland

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Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, , Poland

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Osteo Medic s.c. Artur Racewicz Jerzy Supronik

Bialystok, , Poland

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SNZOZ Lege Artis

Bialystok, , Poland

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Centrum Kliniczno Badawcze

Elblag, , Poland

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Centrum Badan Klinicznych PI-House

Gdansk, , Poland

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Uniwersyteckie Centrum Kliniczne im. prof. Gibinskiego, SUM

Katowice, , Poland

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Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie

Krakow, , Poland

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

Lodz, , Poland

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Gaja Poradnie Lekarskie

Poznan, , Poland

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Centrum Medyczne "Diabetika"

Radom, , Poland

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NBR Polska Tomasz Klodawski

Warsaw, , Poland

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SP CSK Klinika Diabetologii i Chorob Wewnetrznych

Warsaw, , Poland

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Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych I Administracji

Warsaw, , Poland

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Centrum Medyczne Oporow

Wroclaw, , Poland

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Prywatny Gabinet Janusz Gumprecht

Zabrze, , Poland

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Manati Ctr For Clin Research

Manatí, , Puerto Rico

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DIADA, s.r.o.

Bardejov, , Slovakia

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Diabetologicka ambulancia Diabetes care, s.r.o.

Hnúšťa, , Slovakia

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Diabetologicka ambulancia DIAMO s.r.o.

Kežmarok, , Slovakia

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MOMED, s.r.o

Kráľovský Chlmec, , Slovakia

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IN-DIA s.r.o.

Lučenec, , Slovakia

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

Martin, , Slovakia

Site Status

DIABETOL, s.r.o.

Prešov, , Slovakia

Site Status

OLIVER - MED s.r.o.

Rimavská Sobota, , Slovakia

Site Status

MEDI-DIA s.r.o.

Sabinov, , Slovakia

Site Status

Diabetologicka ambulancia MUDr. Gabriela Zimova

Spišská Nová Ves, , Slovakia

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General Hospital Celje

Celje, , Slovenia

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Healthcare Centre Koper

Koper, , Slovenia

Site Status

UKC Ljubljana, Endocrinology and Diabetes

Ljubljana, , Slovenia

Site Status

UKC Maribor - diabetes

Maribor, , Slovenia

Site Status

Healthcare Centre Nova Gorica

Nova Gorica, , Slovenia

Site Status

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status

National Cheng Kung University Hospital

Tainan, , Taiwan

Site Status

Countries

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United States Australia Bulgaria Canada Croatia Czechia Estonia Germany Hungary India Poland Puerto Rico Slovakia Slovenia Taiwan

References

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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.

Reference Type RESULT
PMID: 37385279 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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U1111-1247-0210

Identifier Type: OTHER

Identifier Source: secondary_id

2020-000299-39

Identifier Type: REGISTRY

Identifier Source: secondary_id

NN9924-4635

Identifier Type: -

Identifier Source: org_study_id

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