A Research Study to Compare Two Types of Insulin, a New Weekly Insulin, Insulin Icodec and an Available Daily Insulin, Insulin Glargine, Both in Combination With Mealtime Insulin, in People With Type 2 Diabetes Who Use Daily Insulin and Mealtime Insulin (ONWARDS 4) (ONWARDS 4)

A 26-week Trial Comparing the Effect and Safety of Once Weekly Insulin Icodec and Once Daily Insulin Glargine 100 Units/mL, Both in Combination With Bolus Insulin With or Without Non-insulin Anti-diabetic Drugs, in Subjects With Type 2 Diabetes on a Basal-bolus Regimen

This study compares insulin icodec (a new insulin taken once a week) to insulin glargine (an insulin taken once daily which is already available on the market) in people with type 2 diabetes.

The study will look at how well insulin icodec taken weekly controls blood sugar compared to insulin glargine 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 glargine that participants will have to inject once a day at the same time every day. Which treatment participants will get is decided by chance. 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 8 months. participants will have 17 clinic visits and 13 phone calls with the study doctor.At 8 clinic visits participants will have blood samples taken. At 4 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 their blood sugar all the time in 3 periods for a total of 13 weeks (about 3 months) during the study.

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 2
• Intervention / Treatment: Drug: Insulin icodec; Drug: Insulin aspart; Drug: Insulin glargine

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

Contacts and Locations

Study Locations

• Belgium
  • Bonheiden, Belgium, 2820
    • Imeldaziekenhuis - Bonheiden - Department of Endocrinology
  • Boussu, Belgium, 7300
    • CHU Helora - Site Warquignies
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc - Serv Endocrinologie - Diabétologie
  • Edegem, Belgium, 2650
    • UZA - UZ Antwerpen - Department of Endocrinology
  • Leuven, Belgium, 3000
    • UZ Leuven - Endocrinology
• India
  • Andhra Pradesh
    • Kurnool, Andhra Pradesh, India, 518002
      • Kurnool Medical Collage
  • Haryana
    • Gurgaon, Haryana, India, 122001
      • Medanta - The Medicity Multi-Speciality Hospital, Gurugram
  • Karnataka
    • Bangalore, Karnataka, India, 560043
      • Bangalore Clinisearch
    • Bangalore, Karnataka, India, 560092
      • Lifecare Hospital and Research Centre
    • Bangalore, Karnataka, India, 560034
      • St.John's Hospital
    • Belagavi, Karnataka, India, 590001
      • Belgaum Diabetes Centre
    • Bengaluru, Karnataka, India, 560 024
      • Manipal Hospital, Hebbal, Bengaluru
  • Kerala
    • Kochi, Kerala, India, 682025
      • Renai Medicity
  • Maharashtra
    • Mumbai, Maharashtra, India, 400010
      • Prince Aly Khan Hospital
    • Mumbai, Maharashtra, India, 400058
      • BSES MG hospital
    • Pune, Maharashtra, India, 411001
      • Grant Medical Foundation
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110017
      • Max Super Speciality Hospital, Saket
    • New Delhi, National Capital Territory of Delhi, India, 110088
      • Fortis Hospital, Shalimar Bagh, New Delhi
  • New Delhi
    • Delhi, New Delhi, India, 110002
      • Maulana Azad Medical College
    • New Dehli, New Delhi, India, 110029
      • All India Institute of Medical Sciences
  • Odisha
    • Cuttack, Odisha, India, 753007
      • S.C.B. Medical College
  • Rajasthan
    • Jaipur, Rajasthan, India, 302006
      • Diabetes, Thyroid and Endocrine Centre
• Italy
  • Bologna, Italy, 40138
    • A.O.Universitaria S.ORSOLA-MALPIGHI - U.O.Endocrinologia e Cura
  • Chieti, Italy, 66100
    • Università degli Studi G. D'Annunzio
  • Roma, Italy, 00161
    • Universita Degli Studi Di Roma La Sapienza - Policlinico Umberto I Medicina Sperimentale
  • Campania
    • Napoli, Campania, Italy, 80138
      • A.O.U. Università Studi della Campania "Luigi Vanvitelli"
  • Cz
    • Catanzaro, Cz, Italy, 88100
      • Azienda Ospedaliero-Universitaria Renato Dulbecco
  • MI
    • Milan, MI, Italy, 20132
      • Istituto Scientifico San Raffaele
• Japan
  • Fukuoka-shi, Fukuoka, Japan, 819-0006
    • Futata Tetsuhiro Clinic Meinohama_Internal medicine
  • Hokkaido, Japan, 062-0007
    • Sasaki Internal Medicine
  • Ibaraki, Japan, 311-0113
    • Naka Kinen Clinic_Internal medicine
  • Kitakyusyu-shi, Fukuoka, Japan, 800-0222
    • Sugimoto Clinic,Internal Medicine
  • Saitama, Japan, 336-0967
    • Shimizu Clinic Fusa
  • Tochigi, Japan, 323-0022
    • Oyama East Clinic_Internal Medicine
  • Tokyo, Japan, 105-8471
    • The Jikei University Hospital Dept of Diabetes, Metabolic
  • Ushiku-shi, Ibaraki, Japan, 300-1207
    • Noritake Clinic
  • Kanagawa, Japan
    • Chigasaki-shi, Kanagawa, Japan, Japan, 253-0044
      • Hayashi Diabetes Clinic_Internal Medicine and Diabetes Medicine
• Mexico
  • Jalisco
    • Zapopan, Jalisco, Mexico, 45116
      • Centro de Investigacion Medica de Occidente S.C.
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Unidad biomedica avanzada monterrey
    • Monterrey, Nuevo León, Mexico, 64460
      • Hospital Universitario Dr. José Eleuterio González_Monterrey
• 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
• Romania
  • Brasov, Romania, 500101
    • Mariodiab Clinic SRL
  • Buzău, Romania, 120203
    • S.C. Medcon S.R.L
  • Galati, Romania, 800578
    • Clinical Emergency Sf. Apostol Andrei Hospital
  • Bucurestii
    • Bucharest, Bucurestii, Romania, 020475
      • Institutul National De Diabet Nutritie Si Boli Metabolice Prof.Dr.N.Paulescu Bucuresti- Ion Movila
  • Dâmbovița County
    • Târgovişte, Dâmbovița County, Romania, 130083
      • Spitalul Judetean de Urgenta Targoviste
  • Mureș County
    • Târgu Mureş, Mureș County, Romania, 540142
      • Sc Mediab Srl
• Russia
  • Arkhangelsk, Russia, 163045
    • Arkhangelsk Regional Clinical Hospital
  • Barnaul, Russia, 656045
    • City Hospital #5
  • Kazan', Russia, 420010
    • KSFMU, Inrereginal Clinical Diagnostic center
  • Kirov, Russia, 610014
    • Kirov Clinical Hospital #7
  • Kursk, Russia, 305016
    • Limited Liability Company "AriVa-Med"
  • Moscow, Russia, 123182
    • City Clinical Hospital №52
  • Moscow, Russia, 125008
    • LLC "Centr Targetnoy Terapii"
  • Novosibirsk, Russia, 630099
    • Limited Law Company "Healthy Family" Medicine Center"
  • Saint Petersburg, Russia, 191119
    • SPb SBHI City Outpatient clinic #37
  • Saratov, Russia, 410039
    • Regional clinical cardiology dispensary
  • Russia
    • Tyumen, Russia, Russia, 625023
      • Tumen State Medical University
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • Lynn Institute of the Ozarks
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
    • Concord, California, United States, 94520
      • John Muir Physicians Network
    • Fresno, California, United States, 93720
      • Valley Research
    • Huntington Beach, California, United States, 92648
      • Diabetes/Lipid Mgmt & Res Ctr
    • Northridge, California, United States, 91325
      • Valley Clinical Trials, Inc.
    • Sacramento, California, United States, 95821
      • Clinical Trials Research_Sacramento_0
    • Tustin, California, United States, 92780
      • Diabetes Research Center
    • Ventura, California, United States, 93003
      • Coastal Metabolic Research Center
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research LLC
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • MedStar Diabetes Institute
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Ctr For Clin Res
    • Plantation, Florida, United States, 33324
      • Clinical Trial Res Assoc,Inc
    • West Palm Beach, Florida, United States, 33401
      • Metabolic Research Institute Inc
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Atlanta VA Medical Center
    • Lawrenceville, Georgia, United States, 30046
      • Physicians Research Assoc. LLC
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East West Med Res Inst
  • Idaho
    • Nampa, Idaho, United States, 83686-6011
      • Saltzer Medical Group Research
  • Indiana
    • Valparaiso, Indiana, United States, 46383
      • Velocity Clin. Res Valparaiso
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
    • Waltham, Massachusetts, United States, 02453
      • MassResearch, LLC
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • Jefferson City Medical Group, PC
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • VA NEB - Western IA Health Stm
    • Omaha, Nebraska, United States, 68114
      • Methodist Physicians Clin
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Palm Research Center Inc-Vegas
  • New York
    • Albany, New York, United States, 12206
      • AMC Community Endocrinology
    • Northport, New York, United States, 11768
      • Northport VA Medical Center_Northport_0
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
    • West Seneca, New York, United States, 14224
      • Southgate Medical Group, LLP
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Mountain Diabetes & Endocrine Center
    • Greenville, North Carolina, United States, 27834
      • Physician's East Endocrinology
  • Ohio
    • Mentor, Ohio, United States, 44060
      • Your Diabetes Endocrine Nutrition Group, Inc.
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University_Portland_0
  • Pennsylvania
    • Indiana, Pennsylvania, United States, 15701
      • Indiana-Armstrong Endocrinology Associates
  • South Carolina
    • Greenville, South Carolina, United States, 29605-4254
      • Prisma Health-Upstate
  • Tennessee
    • Bartlett, Tennessee, United States, 38133
      • AM Diabetes And Endocrinology Center
    • Chattanooga, Tennessee, United States, 37421
      • WR-Clinsearch, LLC
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt Diab Obes Clin Tri
  • Texas
    • Amarillo, Texas, United States, 79106
      • Amarillo Med Spec LLP
    • Austin, Texas, United States, 78749
      • Texas Diabetes & Endocrinology
    • Austin, Texas, United States, 78731
      • Texas Diab & Endo, P.A.
    • Corpus Christi, Texas, United States, 78414
      • Osvaldo A. Brusco MD PA
    • Dallas, Texas, United States, 75231
      • North Texas Endocrine Center
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Res-Dallas
    • Dallas, Texas, United States, 75390-9302
      • UT Southwestern Med Cntr
    • Dallas, Texas, United States, 75226
      • Baylr Sctt White Rs Inst, Endo
    • Fort Worth, Texas, United States, 76113
      • Protenium Clinical Research_Hurst
    • Longview, Texas, United States, 75605
      • DCOL Ctr for Clin Res
  • Washington
    • Olympia, Washington, United States, 98502
      • Capital Clin Res Ctr,LLC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female aged above or equal to 18 years at the time of signing informed consent.
• Diagnosed with type 2 diabetes mellitus (T2D) greater than or equal to 180 days prior to the day of screening.
• Glycated haemoglobin (HbA1c) from 7.0-10.0% (53.0 85.8 mmol/mol) both inclusive at screening confirmed by central laboratory analysis.
• Treated with once daily basal insulin (neutral protamine hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL) and 2-4 daily injections of bolus insulin analog (insulin aspart, faster acting insulin aspart, insulin lispro, insulin glulisine) greater than or equal to 90 days prior to the day of screening with or without any of the following anti-diabetic drugs/regimens with stable doses greater than or equal to 90 days prior to screening:

Metformin / Sulfonylureas / Meglitinides (glinides) / DPP-4 inhibitors / SGLT2 inhibitors / Thiazolidinediones / Alpha-glucosidase inhibitors / Oral combination products (for the allowed individual oral anti-diabetic drugs) / Oral or injectable GLP-1-receptor agonists

• Body mass index (BMI) below or equal to 40.0 kg/m^2.

Exclusion Criteria:

• Any episodes (as declared by the subject or in the medical records.) of diabetic ketoacidosis within 90 days prior to the day of screening.
• Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening.
• Chronic heart failure classified as being in New York Heart Association 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; Participants will get once weekly injections in combination with 2-4 times daily injections of insulin aspart	Drug: Insulin icodec; Participants will receive subcutaneous (s.c.) injections of insulin icodec once weekly for 26 weeks; Drug: Insulin aspart; Participants will receive subcutaneous (s.c.) injections of insulin aspart 2-4 times daily for 26 weeks
Active Comparator: Insulin glargine + insulin aspart; Participants will get once daily injections in combination with 2-4 times daily injections of insulin aspart	Drug: Insulin aspart; Participants will receive subcutaneous (s.c.) injections of insulin aspart 2-4 times daily for 26 weeks; Drug: Insulin glargine; Participants will receive subcutaneous (s.c.) injections of insulin glargine once daily for 26 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Glycated Haemoglobin (HbA1c)	Change in HbA1c from baseline (week 0) to week 26 is presented. The outcome data was evaluated based on the in-trial observation 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) and 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 Fasting Plasma Glucose (FPG)	Change in FPG from baseline (week 0) to week 26 is presented. The outcome data was evaluated based on the in-trial observation 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) and death for participants who died before any of the above.	Baseline (week 0), Week 26
Percentage of Time in Target-range 3.9-10.0 mmol/L (70-180 mg/dL) Using Continuous Glucose Monitoring (CGM) System	Percentage of time in target-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 is presented. Time in target range is defined as 100 times the number of recorded measurements in glycaemic target range 3.9-10.0 mmol/L (70-180 mg/dL), both inclusive, divided by the total number of recorded measurements. The outcome data was evaluated based on the in-trial observation 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) and death for participants who died before any of the above.	From week 22 to week 26
Number of Severe Hypoglycaemic Episodes (Level 3)	Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. The outcome data was evaluated based on the on-treatment observation period. The on-treatment observation 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 of trial visit, the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of the dosing interval for both treatment arms) and the end-date for the in-trial observation period.	From baseline (week 0) to week 31
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL) Confirmed by Blood Glucose (BG) Meter)	Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (<) 3.0 mmol/L (54 mg/dL). The outcome data was evaluated based on the on-treatment observation period. The on-treatment observation 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 of trial visit, the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of the dosing interval for both treatment arms) and the end-date for the in-trial observation period.	From baseline (week 0) to week 31
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3)	Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (<) 3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. The outcome data was evaluated based on the in-trial observation period. The on-treatment observation 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 of trial visit, the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of the dosing interval for both treatment arms) and the end-date for the in-trial observation period.	From baseline (week 0) to week 31
Percentage of Time Spent Below 3.0 mmol/L (54 mg/dL) Using Continuous Glucose Monitoring (CGM) System	Percentage of time spent less than (<) 3.0 mmol/L (54 mg/dL) using CGM system from week 22 to week 26 is presented. The outcome data was evaluated based on the in-trial observation 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) and death for participants who died before any of the above.	From week 22 to week 26
Percentage of Time Spent Above 10 mmol/L (180 mg/dL) Using Continuous Glucose Monitoring (CGM) System	Percentage of time spent > 10 mmol/L (180 mg/dL) using CGM system from week 22 to week 26 is presented. The outcome data was evaluated based on the in-trial observation 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) and death for participants who died before any of the above.	From week 22 to week 26
Mean Weekly Insulin Dose	Estimated mean weekly insulin dose during the last 2 weeks of treatment (from week 24 to week 26) is presented. The outcome data was evaluated based on the on-treatment observation period. The on-treatment observation 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 of trial visit, the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of the dosing interval for both treatment arms) and the end-date for the in-trial observation period.	From week 24 to week 26
Change in Body Weight	Change in body weight from baseline (week 0) to week 26 is presented. The outcome data was evaluated based on the in-trial observation 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) and death for participants who died before any of the above.	Baseline (week 0), Week 26

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 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.
• Mathieu C, Asbjornsdottir B, Bajaj HS, Lane W, Matos ALSA, Murthy S, Stachlewska K, Rosenstock J. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial. Lancet. 2023 Jun 10;401(10392):1929-1940. doi: 10.1016/S0140-6736(23)00520-2. Epub 2023 May 5.
• Riddell MC, Heller S, Carstensen L, Rocha TMP, Kehlet Watt S, Woo VC. The effect of once-weekly insulin icodec vs once-daily basal insulin on physical activity-attributed hypoglycaemia in type 2 diabetes: a post hoc analysis of ONWARDS 1-5. Diabetologia. 2025 Jul;68(7):1416-1422. doi: 10.1007/s00125-025-06414-6. Epub 2025 Apr 5.
• 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.
• Watada H, Asbjornsdottir B, Nishida T, Nishimura R, Yamamoto Y, Yamauchi T, Kadowaki T. Efficacy and safety of once-weekly insulin icodec versus once-daily basal insulin in Japanese individuals with type 2 diabetes: A subgroup analysis of the ONWARDS 1, 2 and 4 trials. Diabetes Obes Metab. 2024 Dec;26(12):5882-5895. doi: 10.1111/dom.15960. Epub 2024 Sep 30.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2021
• Primary Completion (Actual): June 16, 2022
• Study Completion (Actual): June 16, 2022

Study Registration Dates

• First Submitted: May 6, 2021
• First Submitted That Met QC Criteria: May 6, 2021
• First Posted (Actual): May 11, 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; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Insulin, Short-Acting; Insulin Glargine; Insulin Aspart; insulin icodec
• Other Study ID Numbers: NN1436-4480; U1111-1247-5269 (Other Identifier: World Health Organization (WHO)); 2020-000474-16 (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