A Research Study to Compare a New Weekly Insulin, Insulin Icodec, and an Available Daily Insulin, Insulin Degludec, Both in Combination With Mealtime Insulin in People With Type 1 Diabetes (ONWARDS 6)

NCT ID: NCT04848480

Last Updated: 2025-12-04

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

582 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-30

Study Completion Date

2022-12-02

Brief Summary

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This study compares insulin icodec (a new insulin) to insulin degludec (an insulin already available on the market) in people with type 1 diabetes.

The study will look at how well insulin icodec taken weekly controls blood sugar compared to insulin degludec taken daily.

Participants will either get insulin icodec that participants will have to inject once a week on the same day of the week, or insulin degludec that participants will have to inject once a day at the same time every day. Which treatment participants get is decided at random. Participants will also get a mealtime insulin.

The insulin is injected with a needle in a skin fold in the thigh, upper arm or stomach.

The study will last for about 1 year and 2 months. Participants will have 28 clinic visits and 28 phone calls with the study doctor. At 11 clinic visits participants will have blood samples taken.

At 6 clinic visits participants cannot eat or drink (except for water) for 8 hours before the visit.

Participants will be asked to wear a sensor that measures your blood sugar all the time. Participants will be asked to wear it for a total of 57 weeks (around 1 year).

Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

Detailed Description

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Conditions

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Diabetes Mellitus, Type 1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Insulin icodec + insulin aspart

insulin icodec once a week in combination with 2-4 times daily injections of insulin aspart at meal times.

Group Type EXPERIMENTAL

insulin icodec

Intervention Type DRUG

insulin icodec 700 units/mL, subcutaneously (under the skin), solution for injection once weekly

insulin aspart

Intervention Type DRUG

insulin aspart 100 units/mL, subcutaneously (under the skin), solution for injection daily

Insulin degludec + insulin aspart

insulin degludec once a day in combination with 2-4 times daily injections of insulin aspart at meal times.

Group Type ACTIVE_COMPARATOR

insulin degludec

Intervention Type DRUG

insulin degludec 100 units/mL, subcutaneously (under the skin), solution for injection once daily

insulin aspart

Intervention Type DRUG

insulin aspart 100 units/mL, subcutaneously (under the skin), solution for injection daily

Interventions

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insulin icodec

insulin icodec 700 units/mL, subcutaneously (under the skin), solution for injection once weekly

Intervention Type DRUG

insulin degludec

insulin degludec 100 units/mL, subcutaneously (under the skin), solution for injection once daily

Intervention Type DRUG

insulin aspart

insulin aspart 100 units/mL, subcutaneously (under the skin), solution for injection daily

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Male or female aged greater than or equal to 18 years at the time of signing informed consent.
* Diagnosed with type 1 diabetes mellitus greater than or equal to 1 year prior to the day of screening.
* Treated with multiple daily insulin injections (basal and bolus insulin analogue regimes) greater than or equal to 1 year prior to the day of screening.
* HbA1c below10% at screening visit based on analysis from central laboratory.

Exclusion Criteria

* Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening.
* Chronic heart failure classified as New York Heart Association (NYHA) Class IV at screening.
* Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids).
* 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 (1452)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

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Klinik Landstraße

Vienna, , Austria

Site Status

Universitätsklinikum AKH Wien

Vienna, , Austria

Site Status

Klinik Hietzing

Vienna, , Austria

Site Status

Winnipeg Clinic

Winnipeg, Manitoba, Canada

Site Status

Eastern Health Authority

St. John's, Newfoundland and Labrador, Canada

Site Status

Nova Scotia Hlth Halifax

Halifax, Nova Scotia, Canada

Site Status

LMC Clinical Res Thornhill

Concord, Ontario, Canada

Site Status

St. Joseph's Health Care

London, Ontario, Canada

Site Status

Centricity Research LMC

Toronto, Ontario, Canada

Site Status

Ctr de rech Clin de Laval

Laval, Quebec, Canada

Site Status

IRCM

Montreal, Quebec, Canada

Site Status

Centre de recherché du CHUS

Sherbrooke, Quebec, Canada

Site Status

CHU de Quebec-Universite Laval

Québec, , Canada

Site Status

Medizinisches Versorgungszentrum Am Bahnhof Spandau GbR

Berlin, , Germany

Site Status

InnoDiab Forschung GmbH

Essen, , Germany

Site Status

Zentrum für klinische Forschung, Dr. med. Lüdemann

Falkensee, , Germany

Site Status

Diabetologische Gemeinschaftspraxis Dr. Staudenmeyer und Dr. Schiwietz

Lingen, , Germany

Site Status

Die Praxis am Ludwigsplatz

Ludwigshafen, , Germany

Site Status

Uniklinik Schleswig-Holstein - Medizinischen Klinik I am Campus Lübeck

Lübeck, , Germany

Site Status

Institut für Diabetesforschung GmbH Münster - Dr. med. Rose

Münster, , Germany

Site Status

RED-Institut für medizinische Studien und Fortbildung GmbH

Oldenburg I. Holst, , Germany

Site Status

RED-Institut für medizinische Forschung und Fortbildung GmbH

Oldenburg in Holstein, , Germany

Site Status

Zentrum für klinische Studien Alexander Segner

Saint Ingbert-Oberwürzbach, , Germany

Site Status

Diacare diabetes Hormonal Clinic

Ahmedabad, Gujarat, India

Site Status

Calicut Medical College

Kozhikode, Kerala, India

Site Status

All India Institute of Medical Sciences

New Dehli, New Delhi, India

Site Status

Post Graduate Institute of Medical Education & Research

Chandigarh, Punjab, India

Site Status

Fortis Heart Institute and Multispeciality Hospital

Mohali, Punjab, India

Site Status

Care Hospital

Hyderabad, , India

Site Status

Lady Hardinge Medical College

New Delhi, , India

Site Status

Jothydev's Diabetes & Research Center

Thriruvananthapuram, , India

Site Status

Azienda Ospedaliera di Perugia;Ospedale S. Maria della Misericordia

Perugia, Umbria, Italy

Site Status

John Muir Physicians Network

Concord, California, United States

Site Status

Headlands Research California, LLC

Escondido, California, United States

Site Status

Valley Research

Fresno, California, United States

Site Status

Scripps Whittier Diabetes Inst

La Jolla, California, United States

Site Status

Diabetes & Endocrine Associates

La Mesa, California, United States

Site Status

Mills-Peninsula Hlth Services

San Mateo, California, United States

Site Status

Diablo Clinical Research, Inc.

Walnut Creek, California, United States

Site Status

Barbara Davis Center

Aurora, Colorado, United States

Site Status

Creekside Endocrine Associates, PC

Denver, Colorado, United States

Site Status

Christiana Care Health Services, Inc.

Newark, Delaware, United States

Site Status

Northeast Research Institute

Fleming Island, Florida, United States

Site Status

Center For Diabetes & Endo Care

Fort Lauderdale, Florida, United States

Site Status

Hanson Clinical Research Center

Port Charlotte, Florida, United States

Site Status

Northeast Research Institute

Saint Augustine, Florida, United States

Site Status

Physicians Research Assoc. LLC

Lawrenceville, Georgia, United States

Site Status

Endo Res Solutions Inc

Roswell, Georgia, United States

Site Status

Northwestern University_Chicago

Chicago, Illinois, United States

Site Status

The University of Chicago

Chicago, Illinois, United States

Site Status

Cotton-O'Neil Diab & Endo Ctr

Topeka, Kansas, United States

Site Status

Endo and Metab Consultants

Rockville, Maryland, United States

Site Status

Brigham & Women's Hospital

Boston, Massachusetts, United States

Site Status

MassResearch, LLC

Waltham, Massachusetts, United States

Site Status

Minn Center For Obesity Met & Endocrinology

Eagan, Minnesota, United States

Site Status

International Diabetes Center

Minneapolis, Minnesota, United States

Site Status

Jefferson City Medical Group, PC

Jefferson City, Missouri, United States

Site Status

Mercy Research

Springfield, Missouri, United States

Site Status

Methodist Physicians Clin

Omaha, Nebraska, United States

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Palm Research Center Inc-Vegas

Las Vegas, Nevada, United States

Site Status

Southern NH Diabetes and Endo_Nashua

Nashua, New Hampshire, United States

Site Status

John J Shelmet, MD

Lawrenceville, New Jersey, United States

Site Status

AMC Community Endocrinology

Albany, New York, United States

Site Status

Accellacare

Wilmington, North Carolina, United States

Site Status

Prisma Health-Upstate

Greenville, South Carolina, United States

Site Status

Univ Diab & Endo Consultants

Chattanooga, Tennessee, United States

Site Status

Amarillo Med Spec LLP

Amarillo, Texas, United States

Site Status

Texas Diab & Endo, P.A.

Austin, Texas, United States

Site Status

Texas Diab & Endo, P.A.

Austin, Texas, United States

Site Status

Velocity Clinical Res-Dallas

Dallas, Texas, United States

Site Status

North Texas Endocrine Center

Dallas, Texas, United States

Site Status

PlanIt Research, PLLC

Houston, Texas, United States

Site Status

NE Clin Res of San Antonio

San Antonio, Texas, United States

Site Status

Rainier Clin Res Ctr Inc

Renton, Washington, United States

Site Status

Univ.-Klinik für Innere Medizin

Graz, , Austria

Site Status

Univ.-Klinik für Innere Medizin I

Innsbruck, , Austria

Site Status

Fließer-Görzer [Ordination]

Saint Stefan, , Austria

Site Status

Policlinico Mater Domini Università di Catanzaro

Catanzaro, , Italy

Site Status

Azienda Ospedaliero Universitaria Careggi MASTER

Florence, , Italy

Site Status

Osp. San Raffaele Diabetes Research Institute, Dibit 1

Milan, , Italy

Site Status

Policlinico Umberto I Clinica Medica DH Diabetologia

Roma, , Italy

Site Status

Master Centre for Italy

Rome, , Italy

Site Status

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Dipartimento di scienze Mediche e Chirurgiche

Rome, , Italy

Site Status

Seino Internal Medicine Clinic_Internal medicine

Koriyama-shi, Fukushima, Japan, Japan

Site Status

Manda Memorial Hospital_Internal Medicine

Sapporo-shi, Hokkaido, Hokkaido, Japan, Japan

Site Status

Jinnouchi Hospital_Internal Medicine

Kumamoto, Kumamoto, Japan, Japan

Site Status

The Institute of Medical Science, Asahi Life Foundation_Internal Medicine

Chuo-ku, Tokyo, , Japan

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H.E.C Science Clinic

Kanagawa, , Japan

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Yuri Ono Clinic

Sapporo-shi, Hokkaido, , Japan

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Tokyo Women's Medical University_Metabolism and Diabetology

Tokyo, , Japan

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Gelre Ziekenhuizen Apeldoorn

Apeldoorn, , Netherlands

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Rijnstate Ziekenhuis

Arnhem, , Netherlands

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Maxima Medisch Centrum

Eindhoven, , Netherlands

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Bethesda Diabetes Research Center en Bethesda ziekenhuis

Hoogeveen, , Netherlands

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Maastricht Universitair Medisch Centrum

Maastricht, , Netherlands

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Ikazia Ziekenhuis

Rotterdam, , Netherlands

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Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

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Volosevich First City Clinical Hospital

Arkhangelsk, , Russia

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LLC "Clinic of new technologies in Medicine"

Dzerzhinskiy, , Russia

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FSBI 'I.I. Dedov National Medical Research Center of Endocrinology' of the MH of Russia

Moscow, , Russia

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Endocrinological Dispensary of Department of healthcare ser.

Moscow, , Russia

Site Status

Endocrinology Dpt,Post-Graduate Medical Education Faculty

Moscow, , Russia

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SPb SBHI "Snegirev Maternity Hospital No. 6"

Saint Petersburg, , Russia

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City Consultative & Diagnostic Centre #1

Saint Petersburg, , Russia

Site Status

SPb SBHI City Multifield Hospital #2

Saint Petersburg, , Russia

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SPb SBHI City polyclinic #117

Saint Petersburg, , Russia

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LLC "Endocrinolog"

Samara, , Russia

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SHI Saratov City Clinical Hospital #9

Saratov, , Russia

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Saratov regional clinical hospital

Saratov, , Russia

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Voronezh Regional Clinical Consultive-diagnostic Centre

Voronezh, , Russia

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Yaroslavl Regional Hospital

Yaroslavl, , Russia

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Hospital Clinic i Provincial

Barcelona, , Spain

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Hospital Clinico Virgen de la Victoria

Málaga, , Spain

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Hospital Univ. Central de Asturias

Oviedo, , Spain

Site Status

Clínica Nuevas Tecnologías en Diabetes y Endocrinología

Seville, , Spain

Site Status

Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi- Endokrinoloji

Adana, , Turkey (Türkiye)

Site Status

Aydın Adnan Menderes Üniversitesi Hastanesi

Aydin, , Turkey (Türkiye)

Site Status

Şişli Hamidiye Etfal Eğitim ve Araştırma Hastanesi- Seyrantepe Yerleşkesi- Endokrinoloji

Istanbul, , Turkey (Türkiye)

Site Status

Prof. Dr. Cemil Taşcıoğlu Şehir Hastanesi- Endokrinoloji

Istanbul, , Turkey (Türkiye)

Site Status

Haydarpaşa Numune Eğitim ve Araştırma Hastanesi - Endokrinoloji

Istanbul, , Turkey (Türkiye)

Site Status

Erciyes Üniversitesi Hastanesi- Nefroloji

Kayseri, , Turkey (Türkiye)

Site Status

İnönü Üniversitesi Turgut Özal Tıp Merkezi - Kardiyoloji

Malatya, , Turkey (Türkiye)

Site Status

Southmead Hospital

Bristol, , United Kingdom

Site Status

Addenbrooke's Hospital_Cambridge

Cambridge, , United Kingdom

Site Status

Royal Derby Hospital

Derby, , United Kingdom

Site Status

Western General Hospital

Edinburgh, , United Kingdom

Site Status

Royal Surrey County Hospital - Diabetes

Guildford, , United Kingdom

Site Status

Churchill Hospital

Oxford, , United Kingdom

Site Status

Lister Hospital

Stevenage, , United Kingdom

Site Status

Joint Clinical Research Facility - Swansea

Swansea, , United Kingdom

Site Status

Countries

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United States Austria Canada Germany India Italy Japan Netherlands Russia Spain Turkey (Türkiye) United Kingdom

References

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Philis-Tsimikas A, Bajaj HS, Begtrup K, Cailleteau R, Gowda A, Lingvay I, Mathieu C, Russell-Jones D, Rosenstock J. Rationale and design of the phase 3a development programme (ONWARDS 1-6 trials) investigating once-weekly insulin icodec in diabetes. Diabetes Obes Metab. 2023 Feb;25(2):331-341. doi: 10.1111/dom.14871. Epub 2022 Oct 14.

Reference Type RESULT
PMID: 36106652 (View on PubMed)

Mohan V, Kesavadev J, Murthy LS, Anil G, Chandrappa M, Kar S, Mishra S. Efficacy and Safety of Once-Weekly Insulin Icodec in Indian Participants with Diabetes: Results from ONWARDS 1, 4, and 6 Studies. Diabetes Ther. 2025 Nov;16(11):2193-2212. doi: 10.1007/s13300-025-01799-4. Epub 2025 Oct 6.

Reference Type DERIVED
PMID: 41051694 (View on PubMed)

Philis-Tsimikas A, Krogsdahl Bache J, Fu A, Kellerer M, Salvesen-Sykes K, Bain SC. Insights on Hospitalisations from the Phase 3a ONWARDS 1-6 Trials of Once-Weekly Insulin Icodec. Diabetes Ther. 2025 Aug;16(8):1615-1631. doi: 10.1007/s13300-025-01745-4. Epub 2025 Jun 4.

Reference Type DERIVED
PMID: 40465144 (View on PubMed)

Russell-Jones D, Babazono T, Cailleteau R, Engberg S, Irace C, Kjaersgaard MIS, Mathieu C, Rosenstock J, Woo V, Klonoff DC. Once-weekly insulin icodec versus once-daily insulin degludec as part of a basal-bolus regimen in individuals with type 1 diabetes (ONWARDS 6): a phase 3a, randomised, open-label, treat-to-target trial. Lancet. 2023 Nov 4;402(10413):1636-1647. doi: 10.1016/S0140-6736(23)02179-7. Epub 2023 Oct 17.

Reference Type DERIVED
PMID: 37863084 (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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U1111-1251-7315

Identifier Type: OTHER

Identifier Source: secondary_id

2020-002374-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NN1436-4625

Identifier Type: -

Identifier Source: org_study_id

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