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

NCT04770532 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: NN1436-4478U1111-1247-49452020-000454-10
• Study Type: interventional
• Target: 526
• Locations: 9 countries
• Sites: 88

Brief 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. 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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Change in Fasting Plasma Glucose (FPG)

  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

  From week 22 to week 26

• Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in Total Treatment Satisfaction

  Baseline (Week 0), Week 26

• Number of Severe Hypoglycaemic Episodes (Level 3)

  From baseline (week 0) to week 31

• Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter)

  From baseline (week 0) to week 31

Study Arms (2)

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.

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.

Drug: Insulin degludec

Interventions

Insulin degludec DRUG

Participants will receive subcutaneous (s.c.) injections of insulin degludec once daily for 26 weeks

Insulin degludec

Insulin Icodec DRUG

Participants will receive subcutaneous (s.c.) injections of insulin icodec once weekly for 26 weeks

Insulin icodec

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (88)

American Clinical Trials

Buena Park, California, 90620, United States

Location

Cedars-Sinai Medical Group

Encino, California, 91436, United States

Location

Valley Research

Fresno, California, 93720, United States

Location

Diabetes/Lipid Mgmt & Res Ctr

Huntington Beach, California, 92648, United States

Location

Scripps Whittier Diabetes Inst

La Jolla, California, 92037, United States

Location

Clinical Trials Research_Sacramento

Lincoln, California, 95648, United States

Location

Valley Clinical Trials, Inc.

Northridge, California, 91325, United States

Location

Desert Oasis Hlthcr Med Group

Palm Springs, California, 92262, United States

Location

Diablo Clinical Research, Inc.

Walnut Creek, California, 94598, United States

Location

South Broward Research LLC

Miramar, Florida, 33027, United States

Location

Renstar Medical Research

Ocala, Florida, 34470, United States

Location

Atlanta Diabetes Associates

Atlanta, Georgia, 30318, United States

Location

Endo Res Solutions Inc

Roswell, Georgia, 30076, United States

Location

Velocity Clin. Res Valparaiso

Valparaiso, Indiana, 46383, United States

Location

Four Rivers Clinical Research Inc

Paducah, Kentucky, 42001, United States

Location

New Orleans Center for Clinical Research

New Orleans, Louisiana, 70119, United States

Location

Ileana J Tandron APMC

Slidell, Louisiana, 70461-4231, United States

Location

Endo And Metab Cons

Rockville, Maryland, 20852, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115-5804, United States

Location

MassResearch, LLC

Waltham, Massachusetts, 02453, United States

Location

Palm Research Center Inc.

Las Vegas, Nevada, 89148, United States

Location

AMC Community Endocrinology

Albany, New York, 12203, United States

Location

Northport VA Med Ctr Northport

Northport, New York, 11768, United States

Location

Mountain Diabetes & Endocrine Center

Asheville, North Carolina, 28803, United States

Location

PharmQuest Life Sciences LLC

Greensboro, North Carolina, 27408, United States

Location

Accellacare

Wilmington, North Carolina, 28401, United States

Location

Amarillo Med Spec LLP

Amarillo, Texas, 79106, United States

Location

Osvaldo A. Brusco MD PA

Corpus Christi, Texas, 78414, United States

Location

Thyroid, Endocrinology, and Diabetes, PA

Dallas, Texas, 75208, United States

Location

Baylr Sctt White Rs Inst, Endo

Dallas, Texas, 75226, United States

Location

Velocity Clinical Res-Dallas

Dallas, Texas, 75230, United States

Location

UT Southwestern Med Cntr

Dallas, Texas, 75390-9302, United States

Location

Diabetes and Thyroid Ctr of FW

Fort Worth, Texas, 76132, United States

Location

PlanIt Research, PLLC

Houston, Texas, 77079, United States

Location

Sun Research Institute

San Antonio, Texas, 78215, United States

Location

Simcare Medical Research, LLC

Sugar Land, Texas, 77478, United States

Location

Hillcrest Family Health Center

Waco, Texas, 76708, United States

Location

Capital Clin Res Ctr,LLC

Olympia, Washington, 98502, United States

Location

Medical center Medi City 21 OOD

Kyustendil, 2500, Bulgaria

Location

MHAT Med Line Clinic

Plovdiv, 4000, Bulgaria

Location

OCIPSOMCEMD ENDO MED-CONSULT - Dr. Nikolay Botushanov

Plovdiv, 4002, Bulgaria

Location

ASOMCEM - Individual Practice - Dr. Antoanela Slavcheva

Rousse, 7002, Bulgaria

Location

MMA-MHAT Sofia, Clinic of Endocrinology and Metab. Diseases

Sofia, 1606, Bulgaria

Location

UMHAT Sofiamed EAD

Sofia, 1797, Bulgaria

Location

InnoDiab Forschung GmbH

Essen, 45136, Germany

Location

Wendisch/Dahl Hamburg (DZHW)

Hamburg, 22607, Germany

Location

Milek, Hohenmölsen

Hohenmölsen, 06679, Germany

Location

Institut für Diabetesforschung GmbH Münster - Dr. med. Rose

Münster, 48145, Germany

Location

Praxis Dr. med. Wenzl-Bauer

Rehlingen-Siersburg, 66780, Germany

Location

Zentrum für klinische Studien Alexander Segner

Saint Ingbert-Oberwürzbach, 66386, Germany

Location

VvP Kliniken gGmbH Marienhospital Stuttgart - Innere Medizin I

Stuttgart, 70199, Germany

Location

MZM Praxis Drs. Erlinger

Stuttgart, 70378, Germany

Location

Hayashi Diabetes Clinic_Internal Medicine and Diabetes Medicine

Chigasaki-shi, Kanagawa, Japan, 253-0044, Japan

Location

Heiwadai Hospital_Internal Medicine

Miyazaki, Miyazaki, 880-0034, Japan

Location

Tokuyama clinic_Diabetic internal medicine

Chiba, 261-0004, Japan

Location

Futata Tetsuhiro Clinic Meinohama_Internal medicine

Fukuoka-shi, Fukuoka, 819-0006, Japan

Location

Naka Kinen Clinic_Internal medicine

Ibaraki, 311-0113, Japan

Location

Yuri Ono Clinic

Sapporo-shi, Hokkaido, 060-0001, Japan

Location

Oyama East Clinic_Internal Medicine

Tochigi, 323-0022, Japan

Location

Juntendo University Hospital_Tokyo

Tokyo, 113-8431, Japan

Location

Noritake Clinic

Ushiku-shi, Ibaraki, 300-1207, Japan

Location

Centrum Terapii Wspolczesnej J.M. Jasnorzewska S.K.A.

Lodz, 90-338, Poland

Location

NZOZ "DiabMed" Poradnia Diabetologiczna

Poznan, 60-821, Poland

Location

Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych I Administracji

Warsaw, 02-507, Poland

Location

Unidade Local De Saude De Matosinhos E.P.E.

Senhora Da Hora, Matosinhos, Matosinhos, 4464-513, Portugal

Location

Unidade Local De Saude De Almada-Seixal E.P.E. - Hospital Garcia de Orta

Almada, 2805-267, Portugal

Location

Unidade Local de Saúde de Coimbra, E.P.E.

Coimbra, 3000-561, Portugal

Location

Unidade Local De Saude De Lisboa Ocidental E.P.E. - Hospital Egas Moniz

Lisbon, 1349-019, Portugal

Location

Unidade Local de Saúde de Santo António, E.P.E

Porto, 4099-001, Portugal

Location

Unidade Local de Saude de Sao Joao E.P.E

Porto, 4200-319, Portugal

Location

Hospital Luz Arrabida, S.A.

Vila Nova de Gaia, 4400-346, Portugal

Location

Greenacres Hospital

Port Elizabeth, Eastern Cape, 6045, South Africa

Location

Medi-Clinic Bloemfontein

Bloemfontein, Free State, 9301, South Africa

Location

Hemant Makan

Johannesburg, Gauteng, 1827, South Africa

Location

Chris Hani Baragwanath Hospital

Johannesburg, Gauteng, 2013, South Africa

Location

Centre for Diabetes

Johannesburg, Gauteng, 2198, South Africa

Location

Dr A Amod

Durban, KwaZulu-Natal, 4092, South Africa

Location

The Catholic University of Korea, ST. Vincent's Hospital

Suwon, Gyeonggi-do, 16247, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, 13620, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Kangbuk Samsung Hospital

Seoul, 03181, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Nowon Eulji Medical Center, Eulji University

Seoul, 139-827, South Korea

Location

"University Clinic" of Dnipro State Medical University - Endocrinology department

Dnipro, 49038, Ukraine

Location

Department of Medical Service and Rehabilitation of "ARTEM" - day hospital department

Kyiv, 04053, Ukraine

Location

Komisarenko Institute of Endocrinology and Metabolism of NAMSU - Department of paediatric endocrine pathology

Kyiv, 04114, Ukraine

Location

Ternopil Central District Hospital - Outpatient department

Ternopil, 46001, Ukraine

Location

Related Publications (6)

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

  PMID: 36106652 RESULT

• Philis-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.

  PMID: 37148899 RESULT

• 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.

  PMID: 40465144 DERIVED

• 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.

  PMID: 40186685 DERIVED

• Polonsky 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.

  PMID: 39368488 DERIVED

• 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.

  PMID: 39344833 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

insulin degludec; insulin icodec

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Clinical Reporting Office (2834)
• Organization: Novo Nordisk A/S

clinicaltrials@novonordisk.com

(+1) 866-867-7178

Study Officials

• Clinical Transparency (dept. 1452)

  Novo Nordisk A/S

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: February 25, 2021
• Study Start: March 5, 2021
• Primary Completion: January 27, 2022
• Study Completion: March 1, 2022
• Last Updated: December 15, 2025
• Results First Posted: February 20, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

BU (6); US (38); PT (7); UA (4); KR (7); PL (3); JP (9); DE (8); ZA (6)