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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: insulin icodec; Drug: insulin aspart; Drug: insulin degludec

• Study Type: Interventional
• Enrollment (Actual): 582
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Univ.-Klinik für Innere Medizin
  • Innsbruck, Austria, 6020
    • Univ.-Klinik für Innere Medizin I
  • Saint Stefan, Austria, 8511
    • Fließer-Görzer [Ordination]
  • Vienna, Austria, 1030
    • Klinik Landstraße
  • Vienna, Austria, 1090
    • Universitätsklinikum AKH Wien
  • Vienna, Austria, 1130
    • Klinik Hietzing
• Canada
  • Québec, Canada, G1V 4G2
    • CHU de Quebec-Universite Laval
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3C 0N2
      • Winnipeg Clinic
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Eastern Health Authority
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Nova Scotia Hlth Halifax
  • Ontario
    • Concord, Ontario, Canada, L4K 4M2
      • LMC Clinical Res Thornhill
    • London, Ontario, Canada, N6A 4V2
      • St. Joseph's Health Care
    • Toronto, Ontario, Canada, M4G 3E8
      • Centricity Research LMC
  • Quebec
    • Laval, Quebec, Canada, H7T 2P5
      • Ctr de rech Clin de Laval
    • Montreal, Quebec, Canada, H2W 1R7
      • IRCM
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre de Recherche du CHUS
• Germany
  • Berlin, Germany, 13597
    • Medizinisches Versorgungszentrum Am Bahnhof Spandau GbR
  • Essen, Germany, 45136
    • InnoDiab Forschung GmbH
  • Falkensee, Germany, 14612
    • Zentrum für klinische Forschung, Dr. med. Lüdemann
  • Lingen, Germany, 49808
    • Diabetologische Gemeinschaftspraxis Dr. Staudenmeyer und Dr. Schiwietz
  • Ludwigshafen, Germany, 67059
    • Die Praxis am Ludwigsplatz
  • Lübeck, Germany, 23538
    • Uniklinik Schleswig-Holstein - Medizinischen Klinik I am Campus Lübeck
  • Münster, Germany, 48145
    • Institut für Diabetesforschung GmbH Münster - Dr. med. Rose
  • Oldenburg I. Holst, Germany, 23758
    • RED-Institut für medizinische Studien und Fortbildung GmbH
  • Oldenburg in Holstein, Germany, 23758
    • RED-Institut für medizinische Forschung und Fortbildung GmbH
  • Saint Ingbert-Oberwürzbach, Germany, 66386
    • Zentrum für klinische Studien Alexander Segner
• India
  • Hyderabad, India, 600034
    • Care Hospital
  • New Delhi, India, 110001
    • Lady Hardinge Medical College
  • Thriruvananthapuram, India, 695 032
    • Jothydev's Diabetes & Research Center
  • Gujarat
    • Ahmedabad, Gujarat, India, 380 015
      • Diacare diabetes Hormonal Clinic
  • Kerala
    • Kozhikode, Kerala, India, 673008
      • Calicut Medical College
  • New Delhi
    • New Dehli, New Delhi, India, 110029
      • All India Institute of Medical Sciences
  • Punjab
    • Chandigarh, Punjab, India, 160012
      • Post Graduate Institute of Medical Education & Research
    • Mohali, Punjab, India, 160062
      • Fortis Heart Institute and Multispeciality Hospital
• Italy
  • Catanzaro, Italy, 88100
    • Policlinico Mater Domini Università di Catanzaro
  • Florence, Italy, 50134
    • Azienda Ospedaliero Universitaria Careggi MASTER
  • Milan, Italy, 20132
    • Osp. San Raffaele Diabetes Research Institute, Dibit 1
  • Roma, Italy, 00161
    • Policlinico Umberto I Clinica Medica DH Diabetologia
  • Rome, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Dipartimento di scienze Mediche e Chirurgiche
  • Rome, Italy, 00144
    • Master Centre for Italy
  • Umbria
    • Perugia, Umbria, Italy, 06129
      • Azienda Ospedaliera di Perugia;Ospedale S. Maria della Misericordia
• Japan
  • Chuo-ku, Tokyo, Japan, 103-0002
    • The Institute of Medical Science, Asahi Life Foundation_Internal Medicine
  • Kanagawa, Japan, 235-0045
    • H.E.C Science Clinic
  • Sapporo-shi, Hokkaido, Japan, 060-0001
    • Yuri Ono Clinic
  • Tokyo, Japan, 162 8666
    • Tokyo Women's Medical University_Metabolism and Diabetology
  • Fukushima, Japan
    • Koriyama-shi, Fukushima, Japan, Japan, 963-8851
      • Seino Internal Medicine Clinic_Internal medicine
  • Hokkaido, Japan
    • Sapporo-shi, Hokkaido, Hokkaido, Japan, Japan, 060-0062
      • Manda Memorial Hospital_Internal Medicine
  • Kumamoto, Japan
    • Kumamoto, Kumamoto, Japan, Japan, 862-0976
      • Jinnouchi Hospital_Internal Medicine
• Netherlands
  • Apeldoorn, Netherlands, 7334 DZ
    • Gelre Ziekenhuizen Apeldoorn
  • Arnhem, Netherlands, 6815 AD
    • Rijnstate Ziekenhuis
  • Eindhoven, Netherlands, 5631 BM
    • Maxima Medisch Centrum
  • Hoogeveen, Netherlands, 7909 AA
    • Bethesda Diabetes Research Center en Bethesda ziekenhuis
  • Maastricht, Netherlands, 6229 HX
    • Maastricht Universitair Medisch Centrum
  • Rotterdam, Netherlands, 3083 AN
    • Ikazia Ziekenhuis
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht
• Russia
  • Arkhangelsk, Russia, 163001
    • Volosevich First City Clinical Hospital
  • Dzerzhinskiy, Russia, 140091
    • LLC "Clinic of new technologies in Medicine"
  • Moscow, Russia, 117292
    • FSBI 'I.I. Dedov National Medical Research Center of Endocrinology' of the MH of Russia
  • Moscow, Russia, 119034
    • Endocrinological Dispensary of Department of healthcare ser.
  • Moscow, Russia, 123448
    • Endocrinology Dpt,Post-Graduate Medical Education Faculty
  • Saint Petersburg, Russia, 194354
    • City Consultative & Diagnostic Centre #1
  • Saint Petersburg, Russia, 194354
    • SPb SBHI City Multifield Hospital #2
  • Saint Petersburg, Russia, 194358
    • SPb SBHI City polyclinic #117
  • Saint Petersburg, Russia, 191014
    • SPb SBHI "Snegirev Maternity Hospital No. 6"
  • Samara, Russia, 443031
    • LLC "Endocrinolog"
  • Saratov, Russia, 410053
    • Saratov Regional Clinical Hospital
  • Saratov, Russia, 410031
    • SHI Saratov City Clinical Hospital #9
  • Voronezh, Russia, 394018
    • Voronezh Regional Clinical Consultive-diagnostic Centre
  • Yaroslavl, Russia, 150062
    • Yaroslavl Regional Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial
  • Málaga, Spain, 29010
    • Hospital Clínico Virgen de la Victoria
  • Oviedo, Spain, 33011
    • Hospital Univ. Central de Asturias
  • Seville, Spain, 41003
    • Clínica Nuevas Tecnologías en Diabetes y Endocrinología
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01150
    • Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi- Endokrinoloji
  • Aydin, Turkey (Türkiye), 09010
    • Aydın Adnan Menderes Universitesi Hastanesi
  • Istanbul, Turkey (Türkiye), 34400
    • Prof. Dr. Cemil Taşcıoğlu Şehir Hastanesi- Endokrinoloji
  • Istanbul, Turkey (Türkiye), 34371
    • Şişli Hamidiye Etfal Eğitim ve Araştırma Hastanesi- Seyrantepe Yerleşkesi- Endokrinoloji
  • Istanbul, Turkey (Türkiye), 34668
    • Haydarpaşa Numune Eğitim ve Araştırma Hastanesi - Endokrinoloji
  • Kayseri, Turkey (Türkiye), 38039
    • Erciyes Üniversitesi Hastanesi- Nefroloji
  • Malatya, Turkey (Türkiye), 44280
    • İnönü Üniversitesi Turgut Özal Tıp Merkezi - Kardiyoloji
• United Kingdom
  • Bristol, United Kingdom, BS10 5NB
    • Southmead Hospital
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital_Cambridge
  • Derby, United Kingdom, DE1 2QY
    • Royal Derby Hospital
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital
  • Guildford, United Kingdom, GU2 7XX
    • Royal Surrey County Hospital - Diabetes
  • Oxford, United Kingdom, OX3 7LE
    • Churchill Hospital
  • Stevenage, United Kingdom, SG1 4AB
    • Lister Hospital
  • Swansea, United Kingdom, SA2 8PP
    • Joint Clinical Research Facility - Swansea
• United States
  • California
    • Concord, California, United States, 94520
      • John Muir Physicians Network
    • Escondido, California, United States, 92025
      • Headlands Research California, LLC
    • Fresno, California, United States, 93720
      • Valley Research
    • La Jolla, California, United States, 92037
      • Scripps Whittier Diabetes Inst
    • La Mesa, California, United States, 91942
      • Diabetes & Endocrine Associates
    • San Mateo, California, United States, 94401
      • Mills-Peninsula Hlth Services
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Barbara Davis Center
    • Denver, Colorado, United States, 80246
      • Creekside Endocrine Associates, PC
  • Delaware
    • Newark, Delaware, United States, 19713
      • Christiana Care Health Services, Inc.
  • Florida
    • Fleming Island, Florida, United States, 32003
      • Northeast Research Institute
    • Fort Lauderdale, Florida, United States, 33312
      • Center For Diabetes & Endo Care
    • Port Charlotte, Florida, United States, 33952
      • Hanson Clinical Research Center
    • Saint Augustine, Florida, United States, 32080
      • Northeast Research Institute
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Physicians Research Assoc. LLC
    • Roswell, Georgia, United States, 30076
      • Endo Res Solutions Inc
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
    • Chicago, Illinois, United States, 60611
      • Northwestern University_Chicago
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Diab & Endo Ctr
  • Maryland
    • Rockville, Maryland, United States, 20852
      • Endo and Metab Consultants
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
    • Waltham, Massachusetts, United States, 02453
      • MassResearch, LLC
  • Minnesota
    • Eagan, Minnesota, United States, 55123
      • Minn Center For Obesity Met & Endocrinology
    • Minneapolis, Minnesota, United States, 55416
      • International Diabetes Center
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • Jefferson City Medical Group, PC
    • Springfield, Missouri, United States, 65807
      • Mercy Research
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Physicians Clin
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Palm Research Center Inc-Vegas
  • New Hampshire
    • Nashua, New Hampshire, United States, 03060
      • Southern NH Diabetes and Endo_Nashua
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • John J Shelmet, MD
  • New York
    • Albany, New York, United States, 12203
      • AMC Community Endocrinology
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Accellacare
  • South Carolina
    • Greenville, South Carolina, United States, 29605-4254
      • Prisma Health-Upstate
  • Tennessee
    • Chattanooga, Tennessee, United States, 37411
      • Univ Diab & Endo Consultants
  • Texas
    • Amarillo, Texas, United States, 79106
      • Amarillo Med Spec LLP
    • Austin, Texas, United States, 78731
      • Texas Diab & Endo, P.A.
    • Austin, Texas, United States, 78749
      • Texas Diab & Endo, P.A.
    • Dallas, Texas, United States, 75231
      • North Texas Endocrine Center
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Res-Dallas
    • Houston, Texas, United States, 77079
      • PlanIt Research, PLLC
    • San Antonio, Texas, United States, 78233
      • NE Clin Res of San Antonio
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Clin Res Ctr Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin icodec + insulin aspart; insulin icodec once a week in combination with 2-4 times daily injections of insulin aspart at meal times.	Drug: insulin icodec; insulin icodec 700 units/mL, subcutaneously (under the skin), solution for injection once weekly; Drug: insulin aspart; insulin aspart 100 units/mL, subcutaneously (under the skin), solution for injection daily
Active Comparator: Insulin degludec + insulin aspart; insulin degludec once a day in combination with 2-4 times daily injections of insulin aspart at meal times.	Drug: insulin aspart; insulin aspart 100 units/mL, subcutaneously (under the skin), solution for injection daily; Drug: insulin degludec; insulin degludec 100 units/mL, subcutaneously (under the skin), solution for injection once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Glycosylated Haemoglobin (HbA1c) at Week 52	Change in HbA1c from baseline to week 52 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 52
Change in Fasting Plasma Glucose (FPG)	Change in FPG 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
Percentage of Time in Range 3.9-10.0 mmol/L (70-180 Milligrams Per Deciliter [mg/dL]) Using Continuous Glucose Monitoring (CGM) System	Percentage of time in range 3.9-10.0 mmol/L (70-180 mg/dL) using CGM system from week 22 to week 26 is presented. Time in range is defined as 100 times the number of recorded measurements in glycaemic range 3.9-10.0 mmol/L (70-180 mg/dL), both inclusive, divided by the total number of recorded measurements. 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.	From week 22 to week 26
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in Total Treatment Satisfaction	Change in DTSQs in total treatment satisfaction from baseline to week 26 is presented. The sum score for DTSQ in total treatment satisfaction was calculated by adding the six item scores of items 1, 4, 5, 6, 7 and 8. The sum score for DTSQ can range from 0 to 36, with 0 being the lowest and 36 being the highest score in total treatment satisfaction. Higher scores on the DTSQ total score indicate higher treatment satisfaction. 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
Mean Total Weekly Insulin Dose: From Week 24 to Week 26	Mean total weekly insulin dose from week 24 to week 26 is presented. Data is reported for 'main-on-treatment' period. The main-on-treatment period started at the date of first dose of trial product as recorded on the eCRF, and ended at the first date of any of the following: the end date of the on-treatment period; week 26. The on-treatment period: Onset date on or after the first dose of trial product and no later than the first date of either the follow-up visit (FU2), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin or the end-date for the in-trial period.	From week 24 to week 26
Mean Total Weekly Insulin Dose: From Week 50 to Week 52	Mean total weekly insulin dose from week 50 to week 52 is presented. Data is reported for 'on-treatment' period. The on-treatment period: Onset date on or after the first dose of trial product and no later than the first date of either the follow-up visit (FU2), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin or the end-date for the in-trial period.	From week 50 to week 52
Change in Body Weight	Change in body weight 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
Number of Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 26	Number of severe hypoglycaemic episodes (level 3) from baseline to week 26 are presented. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. Data is reported for 'main-on-treatment' period. The main-on-treatment period started at the date of first dose of trial product as recorded on the electronic case report form (eCRF), and ended at the first date of any of the following: the end date of the on-treatment period; week 26. On-treatment: Onset date on or after the first dose of trial product and no later than the first date of either the follow-up visit, the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin or the end-date for the in-trial period. Data reflects total number of episodes across all participants within the arm.	From baseline (week 0) to week 26
Number of Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 57	Number of severe hypoglycaemic episodes (level 3) from baseline to week 57 are presented. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. Data is reported for 'on-treatment' period. The on-treatment period: Onset date on or after the first dose of trial product and no later than the first date of either the follow-up visit (FU2), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin or the end-date for the in-trial period. Data reflects total number of episodes across all participants within the arm.	From baseline (week 0) to week 57
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL) Confirmed by Blood Glucose [BG] Meter): From Baseline (Week 0) to Week 26	Number of clinically significant hypoglycaemic episodes (level 2) from baseline to week 26 are presented. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of less than (<) 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Data is reported for 'main-on-treatment' period. The main-on-treatment period started at the date of first dose of trial product as recorded on the eCRF, and ended at the first date of any of the following: the end date of the on-treatment period; week 26. The on-treatment period: Onset date on or after the first dose of trial product and no later than the first date of either the follow-up visit (FU2), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin or the end-date for the in-trial period. Data reflects total number of episodes across all participants within the arm.	From baseline (week 0) to week 26
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL) Confirmed by BG Meter): From Baseline (Week 0) to Week 57	Number of clinically significant hypoglycaemic episodes (level 2) from baseline to week 57 are presented. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of less than (<) 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Data is reported for 'on-treatment' period. The on-treatment period: Onset date on or after the first dose of trial product and no later than the first date of either the follow-up visit (FU2), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin or the end-date for the in-trial period. Data reflects total number of episodes across all participants within the arm.	From baseline (week 0) to week 57
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 26	Number of clinically significant hypoglycaemic episodes (level 2) or severe hypoglycaemic episodes (level 3) from baseline to week 26 presented. Clinically significant hypoglycaemia (level 2) is de-fined as plasma glucose value of < 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Severe hypo-glycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring ex-ternal assistance for recovery. Data is reported for 'main-on-treatment' period, started at date of first dose of trial product as recorded on eCRF, and ended at first date of any of following: end date of on-treatment period; week 26. On-treatment period: Onset date on or after the first dose of trial product and no later than first date of either the follow-up visit (FU2), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin or the end-date for the in-trial period. Data reflects total number of episodes across all participants within the arm.	From baseline (week 0) to week 26
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 57	Number of clinically significant hypoglycaemic episodes (level 2) or severe hypoglycaemic episodes (level 3) from baseline to week 57 are presented. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of less than (<) 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. Data is reported for 'on-treatment' period. The on-treatment period: Onset date on or after the first dose of trial product and no later than the first date of either the follow-up visit (FU2), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin or the end-date for the in-trial period. Data reflects total number of episodes across all participants within the arm.	From baseline (week 0) to week 57
Number of Nocturnal Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 26	Number of nocturnal clinically significant hypoglycaemic episodes (level 2) or severe hypogly-caemic episodes (level 3) from baseline to week 26 presented. Nocturnal: Period between 00:01 and 05:59 (both included). Clinically significant hypoglycaemia (level 2): Plasma glucose value of < 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Severe hypoglycaemia (level 3): Hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. Data is reported for 'main-on-treatment' period, started at date of first dose of trial product as recorded on eCRF, and ended at first date of any of following: end date of on-treatment period; week 26. On-treatment period: Onset date on or after first dose of trial product and no later than first date of either fol-low-up visit, last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin or end-date for in-trial period. Data reflects total number of episodes across all participants within the arm.	From baseline (week 0) to week 26
Number of Nocturnal Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 57	Number of nocturnal clinically significant hypoglycaemic episodes (level 2) or severe hypoglycaemic episodes (level 3) from baseline to week 57 are presented. Nocturnal: The period between 00:01 and 05:59 (both included). Clinically significant hypoglycaemia (level 2): Plasma glucose value of < 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Severe hypoglycaemia (level 3): Hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. Data is reported for 'on-treatment' period. The on-treatment period: Onset date on or after the first dose of trial product and no later than the first date of either the follow-up visit (FU2), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin or the end-date for the in-trial period. Data reflects total number of episodes across all participants within the arm.	From baseline (week 0) to week 57
Percentage of Time Spent Less Than (<) 3.0 mmol/L (54 mg/dL) Using Continuous Glucose Monitoring (CGM) System	Percentage of time spent < 3.0 mmol/L using CGM system from week 22 to week 26 is presented. Time spent below threshold (< 3.0 mmol/L [54 mg/dL]) was defined as 100 times the number of recorded measurements below the threshold, divided by the total number of recorded measurements. 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.	From week 22 to week 26
Percentage of Time Spent Greater Than (>) 10 mmol/L (180 mg/dL) Using Continuous Glucose Monitoring (CGM) System	Percentage of time spent > 10 mmol/L using CGM system from week 22 to week 26 is presented. Time spent above threshold (> 10 mmol/L [180 mg/dL]) was defined as 100 times the number of recorded measurements above the threshold, divided by the total number of recorded measurements. 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.	From week 22 to week 26

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (1452), Novo Nordisk A/S

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2021
• Primary Completion (Actual): April 28, 2022
• Study Completion (Actual): December 2, 2022

Study Registration Dates

• First Submitted: April 16, 2021
• First Submitted That Met QC Criteria: April 16, 2021
• First Posted (Actual): April 19, 2021

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 27, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 1; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Insulins; Pancreatic Hormones; Insulin, Short-Acting; Insulin Aspart; insulin icodec; insulin degludec
• Other Study ID Numbers: NN1436-4625; U1111-1251-7315 (Other Identifier: World Health Organization (WHO)); 2020-002374-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No