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)
ONWARDS 6
Efficacy and Safety of Once Weekly Insulin Icodec Compared to Once Daily Insulin Degludec 100 Units/mL, Both in Combination With Insulin Aspart, in Adults With Type 1 Diabetes. A 26-week, Randomised, Multicentre, Open-label, Active-controlled, Parallel Group, Two Armed, Treat-to-target Trial Investigating the Effect on Glycaemic Control and Safety of Treatment With Once Weekly Insulin Icodec Compared to Once Daily Insulin Degludec, Both in Combination With Insulin Aspart in Adults With Type 1 Diabetes, With a 26-week Extension Investigating Long Term Safety
3 other identifiers
interventional
582
12 countries
130
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Apr 2021
130 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 16, 2021
CompletedFirst Posted
Study publicly available on registry
April 19, 2021
CompletedStudy Start
First participant enrolled
April 30, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 28, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
December 2, 2022
CompletedResults Posted
Study results publicly available
June 12, 2025
CompletedDecember 4, 2025
November 1, 2025
12 months
April 16, 2021
April 23, 2025
November 27, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Change in Glycosylated Haemoglobin (HbA1c) at Week 26
Change in HbA1c from baseline to week 26 is presented. Data is reported for 'in-trial' period. In-trial observation period started at randomisation and ended at the date of: the last direct participant-site contact; withdrawal for participants who withdrew their informed consent; the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e. possibly an unscheduled phone visit); death for participants who died before any of the above.
Baseline (week 0), week 26
Secondary Outcomes (17)
Change in Glycosylated Haemoglobin (HbA1c) at Week 52
Baseline (week 0), week 52
Change in Fasting Plasma Glucose (FPG)
Baseline (week 0), week 26
Percentage of Time in Range 3.9-10.0 mmol/L (70-180 Milligrams Per Deciliter [mg/dL]) Using Continuous Glucose Monitoring (CGM) System
From week 22 to week 26
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in Total Treatment Satisfaction
Baseline (week 0), week 26
Number of Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 26
From baseline (week 0) to week 26
- +12 more secondary outcomes
Study Arms (2)
Insulin icodec + insulin aspart
EXPERIMENTALinsulin icodec once a week in combination with 2-4 times daily injections of insulin aspart at meal times.
Insulin degludec + insulin aspart
ACTIVE COMPARATORinsulin degludec once a day in combination with 2-4 times daily injections of insulin aspart at meal times.
Interventions
insulin icodec 700 units/mL, subcutaneously (under the skin), solution for injection once weekly
insulin degludec 100 units/mL, subcutaneously (under the skin), solution for injection once daily
insulin aspart 100 units/mL, subcutaneously (under the skin), solution for injection daily
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Novo Nordisk A/Slead
Study Sites (130)
John Muir Physicians Network
Concord, California, 94520, United States
Headlands Research California, LLC
Escondido, California, 92025, United States
Valley Research
Fresno, California, 93720, United States
Scripps Whittier Diabetes Inst
La Jolla, California, 92037, United States
Diabetes & Endocrine Associates
La Mesa, California, 91942, United States
Mills-Peninsula Hlth Services
San Mateo, California, 94401, United States
Diablo Clinical Research, Inc.
Walnut Creek, California, 94598, United States
Barbara Davis Center
Aurora, Colorado, 80045, United States
Creekside Endocrine Associates, PC
Denver, Colorado, 80246, United States
Christiana Care Health Services, Inc.
Newark, Delaware, 19713, United States
Northeast Research Institute
Fleming Island, Florida, 32003, United States
Center For Diabetes & Endo Care
Fort Lauderdale, Florida, 33312, United States
Hanson Clinical Research Center
Port Charlotte, Florida, 33952, United States
Northeast Research Institute
Saint Augustine, Florida, 32080, United States
Physicians Research Assoc. LLC
Lawrenceville, Georgia, 30046, United States
Endo Res Solutions Inc
Roswell, Georgia, 30076, United States
Northwestern University_Chicago
Chicago, Illinois, 60611, United States
The University of Chicago
Chicago, Illinois, 60637, United States
Cotton-O'Neil Diab & Endo Ctr
Topeka, Kansas, 66606, United States
Endo and Metab Consultants
Rockville, Maryland, 20852, United States
Brigham & Women's Hospital
Boston, Massachusetts, 02115, United States
MassResearch, LLC
Waltham, Massachusetts, 02453, United States
Minn Center For Obesity Met & Endocrinology
Eagan, Minnesota, 55123, United States
International Diabetes Center
Minneapolis, Minnesota, 55416, United States
Jefferson City Medical Group, PC
Jefferson City, Missouri, 65109, United States
Mercy Research
Springfield, Missouri, 65807, United States
Methodist Physicians Clin
Omaha, Nebraska, 68114, United States
Palm Research Center Inc-Vegas
Las Vegas, Nevada, 89128, United States
Southern NH Diabetes and Endo_Nashua
Nashua, New Hampshire, 03060, United States
John J Shelmet, MD
Lawrenceville, New Jersey, 08648, United States
AMC Community Endocrinology
Albany, New York, 12203, United States
Accellacare
Wilmington, North Carolina, 28401, United States
Prisma Health-Upstate
Greenville, South Carolina, 29605-4254, United States
Univ Diab & Endo Consultants
Chattanooga, Tennessee, 37411, United States
Amarillo Med Spec LLP
Amarillo, Texas, 79106, United States
Texas Diab & Endo, P.A.
Austin, Texas, 78731, United States
Texas Diab & Endo, P.A.
Austin, Texas, 78749, United States
Velocity Clinical Res-Dallas
Dallas, Texas, 75230, United States
North Texas Endocrine Center
Dallas, Texas, 75231, United States
PlanIt Research, PLLC
Houston, Texas, 77079, United States
NE Clin Res of San Antonio
San Antonio, Texas, 78233, United States
Rainier Clin Res Ctr Inc
Renton, Washington, 98057, United States
Univ.-Klinik für Innere Medizin
Graz, 8036, Austria
Univ.-Klinik für Innere Medizin I
Innsbruck, 6020, Austria
Fließer-Görzer [Ordination]
Saint Stefan, 8511, Austria
Klinik Landstraße
Vienna, 1030, Austria
Universitätsklinikum AKH Wien
Vienna, 1090, Austria
Klinik Hietzing
Vienna, 1130, Austria
Winnipeg Clinic
Winnipeg, Manitoba, R3C 0N2, Canada
Eastern Health Authority
St. John's, Newfoundland and Labrador, A1B 3V6, Canada
Nova Scotia Hlth Halifax
Halifax, Nova Scotia, B3H 1V7, Canada
LMC Clinical Res Thornhill
Concord, Ontario, L4K 4M2, Canada
St. Joseph's Health Care
London, Ontario, N6A 4V2, Canada
Centricity Research LMC
Toronto, Ontario, M4G 3E8, Canada
Ctr de rech Clin de Laval
Laval, Quebec, H7T 2P5, Canada
IRCM
Montreal, Quebec, H2W 1R7, Canada
Centre de recherché du CHUS
Sherbrooke, Quebec, J1H 5N4, Canada
CHU de Quebec-Universite Laval
Québec, G1V 4G2, Canada
Medizinisches Versorgungszentrum Am Bahnhof Spandau GbR
Berlin, 13597, Germany
InnoDiab Forschung GmbH
Essen, 45136, Germany
Zentrum für klinische Forschung, Dr. med. Lüdemann
Falkensee, 14612, Germany
Diabetologische Gemeinschaftspraxis Dr. Staudenmeyer und Dr. Schiwietz
Lingen, 49808, Germany
Die Praxis am Ludwigsplatz
Ludwigshafen, 67059, Germany
Uniklinik Schleswig-Holstein - Medizinischen Klinik I am Campus Lübeck
Lübeck, 23538, Germany
Institut für Diabetesforschung GmbH Münster - Dr. med. Rose
Münster, 48145, Germany
RED-Institut für medizinische Studien und Fortbildung GmbH
Oldenburg I. Holst, 23758, Germany
RED-Institut für medizinische Forschung und Fortbildung GmbH
Oldenburg in Holstein, 23758, Germany
Zentrum für klinische Studien Alexander Segner
Saint Ingbert-Oberwürzbach, 66386, Germany
Diacare diabetes Hormonal Clinic
Ahmedabad, Gujarat, 380 015, India
Calicut Medical College
Kozhikode, Kerala, 673008, India
All India Institute of Medical Sciences
New Dehli, New Delhi, 110029, India
Post Graduate Institute of Medical Education & Research
Chandigarh, Punjab, 160012, India
Fortis Heart Institute and Multispeciality Hospital
Mohali, Punjab, 160062, India
Care Hospital
Hyderabad, 600034, India
Lady Hardinge Medical College
New Delhi, 110001, India
Jothydev's Diabetes & Research Center
Thriruvananthapuram, 695 032, India
Azienda Ospedaliera di Perugia;Ospedale S. Maria della Misericordia
Perugia, Umbria, 06129, Italy
Policlinico Mater Domini Università di Catanzaro
Catanzaro, 88100, Italy
Azienda Ospedaliero Universitaria Careggi MASTER
Florence, 50134, Italy
Osp. San Raffaele Diabetes Research Institute, Dibit 1
Milan, 20132, Italy
Policlinico Umberto I Clinica Medica DH Diabetologia
Roma, 00161, Italy
Master Centre for Italy
Rome, 00144, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Dipartimento di scienze Mediche e Chirurgiche
Rome, 00168, Italy
Seino Internal Medicine Clinic_Internal medicine
Koriyama-shi, Fukushima, Japan, 963-8851, Japan
Manda Memorial Hospital_Internal Medicine
Sapporo-shi, Hokkaido, Hokkaido, Japan, 060-0062, Japan
Jinnouchi Hospital_Internal Medicine
Kumamoto, Kumamoto, Japan, 862-0976, Japan
The Institute of Medical Science, Asahi Life Foundation_Internal Medicine
Chuo-ku, Tokyo, 103-0002, Japan
H.E.C Science Clinic
Kanagawa, 235-0045, Japan
Yuri Ono Clinic
Sapporo-shi, Hokkaido, 060-0001, Japan
Tokyo Women's Medical University_Metabolism and Diabetology
Tokyo, 162 8666, Japan
Gelre Ziekenhuizen Apeldoorn
Apeldoorn, 7334 DZ, Netherlands
Rijnstate Ziekenhuis
Arnhem, 6815 AD, Netherlands
Maxima Medisch Centrum
Eindhoven, 5631 BM, Netherlands
Bethesda Diabetes Research Center en Bethesda ziekenhuis
Hoogeveen, 7909 AA, Netherlands
Maastricht Universitair Medisch Centrum
Maastricht, 6229 HX, Netherlands
Ikazia Ziekenhuis
Rotterdam, 3083 AN, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, 3584 CX, Netherlands
Volosevich First City Clinical Hospital
Arkhangelsk, 163001, Russia
LLC "Clinic of new technologies in Medicine"
Dzerzhinskiy, 140091, Russia
FSBI 'I.I. Dedov National Medical Research Center of Endocrinology' of the MH of Russia
Moscow, 117292, Russia
Endocrinological Dispensary of Department of healthcare ser.
Moscow, 119034, Russia
Endocrinology Dpt,Post-Graduate Medical Education Faculty
Moscow, 123448, Russia
SPb SBHI "Snegirev Maternity Hospital No. 6"
Saint Petersburg, 191014, Russia
City Consultative & Diagnostic Centre #1
Saint Petersburg, 194354, Russia
SPb SBHI City Multifield Hospital #2
Saint Petersburg, 194354, Russia
SPb SBHI City polyclinic #117
Saint Petersburg, 194358, Russia
LLC "Endocrinolog"
Samara, 443031, Russia
SHI Saratov City Clinical Hospital #9
Saratov, 410031, Russia
Saratov regional clinical hospital
Saratov, 410053, Russia
Voronezh Regional Clinical Consultive-diagnostic Centre
Voronezh, 394018, Russia
Yaroslavl Regional Hospital
Yaroslavl, 150062, Russia
Hospital Clinic i Provincial
Barcelona, 08036, Spain
Hospital Clinico Virgen de la Victoria
Málaga, 29010, Spain
Hospital Univ. Central de Asturias
Oviedo, 33011, Spain
Clínica Nuevas Tecnologías en Diabetes y Endocrinología
Seville, 41003, Spain
Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi- Endokrinoloji
Adana, 01150, Turkey (Türkiye)
Aydın Adnan Menderes Üniversitesi Hastanesi
Aydin, 09010, Turkey (Türkiye)
Şişli Hamidiye Etfal Eğitim ve Araştırma Hastanesi- Seyrantepe Yerleşkesi- Endokrinoloji
Istanbul, 34371, Turkey (Türkiye)
Prof. Dr. Cemil Taşcıoğlu Şehir Hastanesi- Endokrinoloji
Istanbul, 34400, Turkey (Türkiye)
Haydarpaşa Numune Eğitim ve Araştırma Hastanesi - Endokrinoloji
Istanbul, 34668, Turkey (Türkiye)
Erciyes Üniversitesi Hastanesi- Nefroloji
Kayseri, 38039, Turkey (Türkiye)
İnönü Üniversitesi Turgut Özal Tıp Merkezi - Kardiyoloji
Malatya, 44280, Turkey (Türkiye)
Southmead Hospital
Bristol, BS10 5NB, United Kingdom
Addenbrooke's Hospital_Cambridge
Cambridge, CB2 0QQ, United Kingdom
Royal Derby Hospital
Derby, DE1 2QY, United Kingdom
Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
Royal Surrey County Hospital - Diabetes
Guildford, GU2 7XX, United Kingdom
Churchill Hospital
Oxford, OX3 7LE, United Kingdom
Lister Hospital
Stevenage, SG1 4AB, United Kingdom
Joint Clinical Research Facility - Swansea
Swansea, SA2 8PP, United Kingdom
Related Publications (4)
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.
PMID: 36106652RESULTMohan 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.
PMID: 41051694DERIVEDPhilis-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.
PMID: 40465144DERIVEDRussell-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.
PMID: 37863084DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Reporting Office (2834)
- Organization
- Novo Nordisk A/S
Study Officials
- STUDY DIRECTOR
Clinical Transparency (1452)
Novo Nordisk A/S
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 16, 2021
First Posted
April 19, 2021
Study Start
April 30, 2021
Primary Completion
April 28, 2022
Study Completion
December 2, 2022
Last Updated
December 4, 2025
Results First Posted
June 12, 2025
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will share
According to the Novo Nordisk disclosure commitment on novonordisk-trials.com