Diabetes Mellitus, Type 2Phase 3ONWARDS 2NCT04770532
A Research Study to Compare Two Types of Insulin, a New Weekly Insulin, Insulin Icodec and an Available Daily Insulin, Insulin Degludec, in People With Type 2 Diabetes Who Use Daily Insulin
A Phase 3 study testing Insulin degludec and Insulin Icodec in people with Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 88 sites in 9 countries.
Trial summary
This study compares insulin icodec (a new insulin taken once a week) to insulin degludec (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 degludec taken daily. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Insulin degludec and Insulin Icodec
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 526 participants
- Where
- 88 sitesin 9 countries
- Study dates
- 5 Mar 2021to 1 Mar 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female aged above or equal to 18 years at the time of signing informed consent.
- Diagnosed with T2D greater than or equal to 180 days prior to the day of screening.
- 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 or twice daily basal insulin (Neutral Protamine Hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL): 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
Show all 14Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
88 sites in 9 countries.
88 sites in 9 countries
United States38 sites
AMC Community Endocrinology
Albany, New York, 12203
Amarillo Med Spec LLP
Amarillo, Texas, 79106
Mountain Diabetes & Endocrine Center
Asheville, North Carolina, 28803
Atlanta Diabetes Associates
Atlanta, Georgia, 30318
Brigham & Women's Hospital
Boston, Massachusetts, 02115-5804
American Clinical Trials
Buena Park, California, 90620
Osvaldo A. Brusco MD PA
Corpus Christi, Texas, 78414
Thyroid, Endocrinology, and Diabetes, PA
Dallas, Texas, 75208
Baylr Sctt White Rs Inst, Endo
Dallas, Texas, 75226
Velocity Clinical Res-Dallas
Dallas, Texas, 75230
UT Southwestern Med Cntr
Dallas, Texas, 75390-9302
Cedars-Sinai Medical Group
Encino, California, 91436
Diabetes and Thyroid Ctr of FW
Fort Worth, Texas, 76132
Valley Research
Fresno, California, 93720
PharmQuest Life Sciences LLC
Greensboro, North Carolina, 27408
PlanIt Research, PLLC
Houston, Texas, 77079
Diabetes/Lipid Mgmt & Res Ctr
Huntington Beach, California, 92648
Scripps Whittier Diabetes Inst
La Jolla, California, 92037
Palm Research Center Inc.
Las Vegas, Nevada, 89148
Clinical Trials Research_Sacramento
Lincoln, California, 95648
South Broward Research LLC
Miramar, Florida, 33027
New Orleans Center for Clinical Research
New Orleans, Louisiana, 70119
Northport VA Med Ctr Northport
Northport, New York, 11768
Valley Clinical Trials, Inc.
Northridge, California, 91325
Renstar Medical Research
Ocala, Florida, 34470
Capital Clin Res Ctr,LLC
Olympia, Washington, 98502
Four Rivers Clinical Research Inc
Paducah, Kentucky, 42001
Desert Oasis Hlthcr Med Group
Palm Springs, California, 92262
Endo And Metab Cons
Rockville, Maryland, 20852
Endo Res Solutions Inc
Roswell, Georgia, 30076
Sun Research Institute
San Antonio, Texas, 78215
Ileana J Tandron APMC
Slidell, Louisiana, 70461-4231
Simcare Medical Research, LLC
Sugar Land, Texas, 77478
Velocity Clin. Res Valparaiso
Valparaiso, Indiana, 46383
Hillcrest Family Health Center
Waco, Texas, 76708
Diablo Clinical Research, Inc.
Walnut Creek, California, 94598
MassResearch, LLC
Waltham, Massachusetts, 02453
Accellacare
Wilmington, North Carolina, 28401
Japan9 sites
Tokuyama clinic_Diabetic internal medicine
Chiba, 261-0004
Hayashi Diabetes Clinic_Internal Medicine and Diabetes Medicine
Chigasaki-shi, Kanagawa, Japan, 253-0044
Futata Tetsuhiro Clinic Meinohama_Internal medicine
Fukuoka-shi, Fukuoka, 819-0006
Naka Kinen Clinic_Internal medicine
Ibaraki, 311-0113
Heiwadai Hospital_Internal Medicine
Miyazaki, Miyazaki, 880-0034
Yuri Ono Clinic
Sapporo-shi, Hokkaido, 060-0001
Oyama East Clinic_Internal Medicine
Tochigi, 323-0022
Juntendo University Hospital_Tokyo
Tokyo, 113-8431
Noritake Clinic
Ushiku-shi, Ibaraki, 300-1207
Germany8 sites
InnoDiab Forschung GmbH
Essen, 45136
Wendisch/Dahl Hamburg (DZHW)
Hamburg, 22607
Milek, Hohenmölsen
Hohenmölsen, 06679
Institut für Diabetesforschung GmbH Münster - Dr. med. Rose
Münster, 48145
Praxis Dr. med. Wenzl-Bauer
Rehlingen-Siersburg, 66780
Zentrum für klinische Studien Alexander Segner
Saint Ingbert-Oberwürzbach, 66386
VvP Kliniken gGmbH Marienhospital Stuttgart - Innere Medizin I
Stuttgart, 70199
MZM Praxis Drs. Erlinger
Stuttgart, 70378
Portugal7 sites
Unidade Local De Saude De Almada-Seixal E.P.E. - Hospital Garcia de Orta
Almada, 2805-267
Unidade Local de Saúde de Coimbra, E.P.E.
Coimbra, 3000-561
Unidade Local De Saude De Lisboa Ocidental E.P.E. - Hospital Egas Moniz
Lisbon, 1349-019
Unidade Local de Saúde de Santo António, E.P.E
Porto, 4099-001
Unidade Local de Saude de Sao Joao E.P.E
Porto, 4200-319
Unidade Local De Saude De Matosinhos E.P.E.
Senhora Da Hora, Matosinhos, Matosinhos, 4464-513
Hospital Luz Arrabida, S.A.
Vila Nova de Gaia, 4400-346
South Korea7 sites
Seoul National University Bundang Hospital
Gyeonggi-do, 13620
Korea University Anam Hospital
Seoul, 02841
Seoul National University Hospital
Seoul, 03080
Kangbuk Samsung Hospital
Seoul, 03181
Severance Hospital, Yonsei University Health System
Seoul, 03722
Nowon Eulji Medical Center, Eulji University
Seoul, 139-827
The Catholic University of Korea, ST. Vincent's Hospital
Suwon, Gyeonggi-do, 16247
Bulgaria6 sites
Medical center Medi City 21 OOD
Kyustendil, 2500
MHAT Med Line Clinic
Plovdiv, 4000
OCIPSOMCEMD ENDO MED-CONSULT - Dr. Nikolay Botushanov
Plovdiv, 4002
ASOMCEM - Individual Practice - Dr. Antoanela Slavcheva
Rousse, 7002
MMA-MHAT Sofia, Clinic of Endocrinology and Metab. Diseases
Sofia, 1606
UMHAT Sofiamed EAD
Sofia, 1797
South Africa6 sites
Medi-Clinic Bloemfontein
Bloemfontein, Free State, 9301
Dr A Amod
Durban, KwaZulu-Natal, 4092
Hemant Makan
Johannesburg, Gauteng, 1827
Chris Hani Baragwanath Hospital
Johannesburg, Gauteng, 2013
Centre for Diabetes
Johannesburg, Gauteng, 2198
Greenacres Hospital
Port Elizabeth, Eastern Cape, 6045
Ukraine4 sites
"University Clinic" of Dnipro State Medical University - Endocrinology department
Dnipro, 49038
Department of Medical Service and Rehabilitation of "ARTEM" - day hospital department
Kyiv, 04053
Komisarenko Institute of Endocrinology and Metabolism of NAMSU - Department of paediatric endocrine pathology
Kyiv, 04114
Ternopil Central District Hospital - Outpatient department
Ternopil, 46001
Poland3 sites
Centrum Terapii Wspolczesnej J.M. Jasnorzewska S.K.A.
Lodz, 90-338
NZOZ "DiabMed" Poradnia Diabetologiczna
Poznan, 60-821
Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych I Administracji
Warsaw, 02-507
About this study
Official title: A 26-week Trial Comparing the Effect and Safety of Once Weekly Insulin Icodec and Once Daily Insulin Degludec, Both With or Without Non-insulin Anti-diabetic Drugs, in Subjects With Type 2 Diabetes Treated With Basal Insulin
This study compares insulin icodec (a new insulin taken once a week) to insulin degludec (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 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 by chance.
Read more
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.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Insulin degludec, Insulin Icodec
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin degludecDrug
Participants will receive subcutaneous (s.c.) injections of insulin degludec once daily for 26 weeks
Insulin IcodecDrug
Participants will receive subcutaneous (s.c.) injections of insulin icodec once weekly for 26 weeks
| Study group | Role | What they receive |
|---|---|---|
| Insulin icodec | Experimental | Insulin icodec + non-insulin anti-diabetic drugs. Pre-trial non-insulin anti-diabetic background medication throughout the entire trial except from sulfonylureas and glinides, which must be discontinued at randomisation. The background medication should be maintained at the stable, pre-trial dose and at the same frequency during the entire treatment period. Receives: Drug: Insulin Icodec |
| Insulin degludec | Active comparator | Insulin degludec + non-insulin anti-diabetic drugs. Pre-trial non-insulin anti-diabetic background medication throughout the entire trial except from sulfonylureas and glinides, which must be discontinued at randomisation. The background medication should be maintained at the stable, pre-trial dose and at the same frequency during the entire treatment period. Receives: Drug: Insulin degludec |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (Week 0), Week 26
Secondary outcomes (10)
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.
Measured: Baseline (Week 0), Week 26
Percentage of Time in Target-range 3.9-10.0 Millimoles Per Liter (mmol/L) (70-180 Milligrams Per Deciliter [mg/dL]) Using Continuous Glucose Monitoring (CGM) System
The 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 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.
Measured: 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 (week 0) to week 26 is presented. The DTSQ domain score in total treatment satisfaction was calculated by adding the six item scores of items 1, 4-8. Higher scores indicate higher levels of treatment satisfaction for items 1, 4 -8. For items 2 and 3 a higher score indicates a participant perceived experience of hyperglycaemia and hypoglycaemia. Lower scores indicate a perception of blood glucose levels being unacceptably high (item 2) or low (item 3). The score has a minimum of 0 and a maximum of 36. The outcome data was evaluated based on in-trial observation period. In-trial observation period started at randomisation and ended at the date of: Last direct participant-site contact, withdrawal for participants who withdrew their informed consent, last participant-investigator contact as defined by the investigator for participants who were lost to follow-up and death for participants who died before any of the above.
Measured: Baseline (Week 0), Week 26
Number of Severe Hypoglycaemic Episodes (Level 3)
Number of severe hypoglycaemic episodes (level 3) is presented. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. The outcome data was evaluated based on the on-treatment observation period. The 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 of trial visit (V30), 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. The on-treatment period represented the time period in which a participant was considered exposed to trial product.
Measured: 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)
Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by blood glucose (BG) meter) is 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. The outcome data was evaluated based on the on-treatment observation period. The 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 of trial visit (V30), 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. The on-treatment period represented the time period in which a participant was considered exposed to trial product.
Measured: 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)
Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by blood glucose (BG) meter) or severe hypoglycaemic episodes (level 3) is presented. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of < 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. The outcome data was evaluated based on the in-trial observation period. The 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 of trial visit (V30), 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.
Measured: From baseline (week 0) to week 31
Percentage of Time Spent < 3.0 mmol/L (54 mg/dL) Using Continuous Glucose Monitoring (CGM) System
Percentage of tiime spent < 3.0 millimoles per liter (mmol/L) (54 mg/dL) using continuous glucose monitoring (CGM) system 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.
Measured: From week 22 to week 26
Percentage of Time Spent > 10 mmol/L (180 mg/dL) Using Continuous Glucose Monitoring (CGM) System
Percentage of time spent > 10 millimoles per liter (mmol/L) (180 milligrams per deciliter [mg/dL]) using continuous glucose monitoring (CGM) system 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.
Measured: 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 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 (V30), 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. The on-treatment period represented the time period in which a participant was considered exposed to trial product.
Measured: 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.
Measured: Baseline (Week 0), Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2021
- Study start5 Mar 2021
- Primary completion27 Jan 2022
- Study completion1 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 526 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Transparency (dept. 1452), Study director, Novo Nordisk A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04770532
- Sponsor's protocol ID
- NN1436-4478
- Other IDs
- U1111-1247-4945, 2020-000454-10
- Acronym
- ONWARDS 2
- Status last verified
- Nov 2025
- First submitted
- 22 Feb 2021
- Last updated
- 15 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
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.
PubMed 36106652Philis-Tsimikas A, Asong M, Franek E, Jia T, Rosenstock J, Stachlewska K, Watada H, Kellerer M. Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial. Lancet Diabetes Endocrinol. 2023 Jun;11(6):414-425. doi: 10.1016/S2213-8587(23)00093-1. Epub 2023 May 3.
PubMed 37148899Kristensen NR, Haridas MP, Philis-Tsimikas A, Ribel-Madsen R, Mathieu C. The Effect of Intrinsic Factors on the Pharmacokinetics of Once-Weekly Insulin Icodec in Type 1 and Type 2 Diabetes: A Population Pharmacokinetic Analysis of Phase II and Phase III trials. Clin Pharmacokinet. 2026 Sep 30. doi: 10.1007/s40262-026-01710-9. Online ahead of print.
PubMed 42814374Philis-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.
PubMed 40465144Riddell 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.
PubMed 40186685Polonsky W, Benamar M, Carstensen L, Davies M, Meller Donatsky A, Franek E, Kellerer M, Philis-Tsimikas A, Goldenberg R. Improved treatment satisfaction with once-weekly insulin icodec compared with once-daily basal insulin in individuals with type 2 diabetes: An analysis of patient-reported outcomes and participant interviews from ONWARDS 2 and 5 and a physician survey from ONWARDS 1. Diabetes Res Clin Pract. 2024 Nov;217:111885. doi: 10.1016/j.diabres.2024.111885. Epub 2024 Oct 4.
PubMed 39368488Watada 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.
PubMed 39344833
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 26-week Trial Comparing the Effect and Safety of Once Weekly Insulin Icodec and Once Daily Insulin Degludec, Both With or Without Non-insulin Anti-diabetic Drugs, in Subjects With Type 2 Diabetes Treated With Basal Insulin
- ClinicalTrials.gov ID
- NCT04770532
- Acronym / sponsor ID
- ONWARDS 2 / NN1436-4478
- Conditions
- Diabetes Mellitus, Type 2
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 526 participants (actual)
- Lead sponsor
- Novo Nordisk A/SIndustry (pharma, biotech, devices)
- Study start
- 5 Mar 2021 (actual)
- Primary completion
- 27 Jan 2022 (actual)
- Study completion
- 1 Mar 2022 (actual)
- First posted
- 25 Feb 2021 (actual)
- Results
- Posted 20 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study compares insulin icodec (a new insulin taken once a week) to insulin degludec (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 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 by chance.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Insulin icodec | Experimental | Drug: Insulin IcodecInsulin icodec + non-insulin anti-diabetic drugs. Pre-trial non-insulin anti-diabetic background medication throughout the entire trial except from sulfonylureas and glinides, which must be discontinued at randomisation. The background medication should be maintained at the stable, pre-trial dose and at the same frequency during the entire treatment period. |
| Insulin degludec | Active comparator | Drug: Insulin degludecInsulin degludec + non-insulin anti-diabetic drugs. Pre-trial non-insulin anti-diabetic background medication throughout the entire trial except from sulfonylureas and glinides, which must be discontinued at randomisation. The background medication should be maintained at the stable, pre-trial dose and at the same frequency during the entire treatment period. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- Male or female aged above or equal to 18 years at the time of signing informed consent.
- Diagnosed with T2D greater than or equal to 180 days prior to the day of screening.
- 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 or twice daily basal insulin (Neutral Protamine Hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL): 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:
- Body mass index (BMI) below or equal to 40.0 kg/m^2.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Insulin degludecParticipants will receive subcutaneous (s.c.) injections of insulin degludec once daily for 26 weeks | Drug | Insulin degludec |
| Insulin IcodecParticipants will receive subcutaneous (s.c.) injections of insulin icodec once weekly for 26 weeks | Drug | Insulin icodec |
Primary outcome
Change in Glycated Haemoglobin (HbA1c)
Time frame: Baseline (Week 0), Week 26
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.
10 secondary outcomes
Change in Fasting Plasma Glucose (FPG)
Time frame: Baseline (Week 0), Week 26
Percentage of Time in Target-range 3.9-10.0 Millimoles Per Liter (mmol/L) (70-180 Milligrams Per Deciliter [mg/dL]) Using Continuous Glucose Monitoring (CGM) System
Time frame: From week 22 to week 26
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in Total Treatment Satisfaction
Time frame: Baseline (Week 0), Week 26
Number of Severe Hypoglycaemic Episodes (Level 3)
Time frame: 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)
Time frame: 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)
Time frame: From baseline (week 0) to week 31
Percentage of Time Spent < 3.0 mmol/L (54 mg/dL) Using Continuous Glucose Monitoring (CGM) System
Time frame: From week 22 to week 26
Percentage of Time Spent > 10 mmol/L (180 mg/dL) Using Continuous Glucose Monitoring (CGM) System
Time frame: From week 22 to week 26
Mean Weekly Insulin Dose
Time frame: From week 24 to week 26
Change in Body Weight
Time frame: Baseline (Week 0), Week 26
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 36106652Philis-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.
- Results publication: PubMed 37148899Philis-Tsimikas A, Asong M, Franek E, Jia T, Rosenstock J, Stachlewska K, Watada H, Kellerer M. Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial. Lancet Diabetes Endocrinol. 2023 Jun;11(6):414-425. doi: 10.1016/S2213-8587(23)00093-1. Epub 2023 May 3.
- Derived from this study: PubMed 42814374Kristensen NR, Haridas MP, Philis-Tsimikas A, Ribel-Madsen R, Mathieu C. The Effect of Intrinsic Factors on the Pharmacokinetics of Once-Weekly Insulin Icodec in Type 1 and Type 2 Diabetes: A Population Pharmacokinetic Analysis of Phase II and Phase III trials. Clin Pharmacokinet. 2026 Sep 30. doi: 10.1007/s40262-026-01710-9. Online ahead of print.
- Derived from this study: PubMed 40465144Philis-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.
- Derived from this study: PubMed 40186685Riddell 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.
- Derived from this study: PubMed 39368488Polonsky W, Benamar M, Carstensen L, Davies M, Meller Donatsky A, Franek E, Kellerer M, Philis-Tsimikas A, Goldenberg R. Improved treatment satisfaction with once-weekly insulin icodec compared with once-daily basal insulin in individuals with type 2 diabetes: An analysis of patient-reported outcomes and participant interviews from ONWARDS 2 and 5 and a physician survey from ONWARDS 1. Diabetes Res Clin Pract. 2024 Nov;217:111885. doi: 10.1016/j.diabres.2024.111885. Epub 2024 Oct 4.
- Derived from this study: PubMed 39344833Watada 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.
- Individual participant dataSharing planned: Yes. According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Transparency (dept. 1452) study director
Novo Nordisk A/S
88 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Insulin degludec and Insulin Icodec in people with Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 88 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 88 sites in United States, Japan, Germany, Portugal, South Korea and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Glycated Haemoglobin (HbA1c) (time frame: Baseline (Week 0), Week 26). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04770532, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2025; AzTrials last refreshed its copy on 26 Oct 2026.