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

NCT ID: NCT04770532

Last Updated: 2025-12-15

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

526 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-05

Study Completion Date

2022-03-01

Brief Summary

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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.

Detailed Description

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Conditions

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Diabetes Mellitus, Type 2

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Insulin icodec

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.

Group Type EXPERIMENTAL

Insulin Icodec

Intervention Type DRUG

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

Insulin degludec

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.

Group Type ACTIVE_COMPARATOR

Insulin degludec

Intervention Type DRUG

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

Interventions

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Insulin degludec

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

Intervention Type DRUG

Insulin Icodec

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novo Nordisk A/S

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Transparency (dept. 1452)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

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American Clinical Trials

Buena Park, California, United States

Site Status

Cedars-Sinai Medical Group

Encino, California, United States

Site Status

Valley Research

Fresno, California, United States

Site Status

Diabetes/Lipid Mgmt & Res Ctr

Huntington Beach, California, United States

Site Status

Scripps Whittier Diabetes Inst

La Jolla, California, United States

Site Status

Clinical Trials Research_Sacramento

Lincoln, California, United States

Site Status

Valley Clinical Trials, Inc.

Northridge, California, United States

Site Status

Desert Oasis Hlthcr Med Group

Palm Springs, California, United States

Site Status

Diablo Clinical Research, Inc.

Walnut Creek, California, United States

Site Status

South Broward Research LLC

Miramar, Florida, United States

Site Status

Renstar Medical Research

Ocala, Florida, United States

Site Status

Atlanta Diabetes Associates

Atlanta, Georgia, United States

Site Status

Endo Res Solutions Inc

Roswell, Georgia, United States

Site Status

Velocity Clin. Res Valparaiso

Valparaiso, Indiana, United States

Site Status

Four Rivers Clinical Research Inc

Paducah, Kentucky, United States

Site Status

New Orleans Center for Clinical Research

New Orleans, Louisiana, United States

Site Status

Ileana J Tandron APMC

Slidell, Louisiana, United States

Site Status

Endo And Metab Cons

Rockville, Maryland, United States

Site Status

Brigham & Women's Hospital

Boston, Massachusetts, United States

Site Status

MassResearch, LLC

Waltham, Massachusetts, United States

Site Status

Palm Research Center Inc.

Las Vegas, Nevada, United States

Site Status

AMC Community Endocrinology

Albany, New York, United States

Site Status

Northport VA Med Ctr Northport

Northport, New York, United States

Site Status

Mountain Diabetes & Endocrine Center

Asheville, North Carolina, United States

Site Status

PharmQuest Life Sciences LLC

Greensboro, North Carolina, United States

Site Status

Accellacare

Wilmington, North Carolina, United States

Site Status

Amarillo Med Spec LLP

Amarillo, Texas, United States

Site Status

Osvaldo A. Brusco MD PA

Corpus Christi, Texas, United States

Site Status

Thyroid, Endocrinology, and Diabetes, PA

Dallas, Texas, United States

Site Status

Baylr Sctt White Rs Inst, Endo

Dallas, Texas, United States

Site Status

Velocity Clinical Res-Dallas

Dallas, Texas, United States

Site Status

UT Southwestern Med Cntr

Dallas, Texas, United States

Site Status

Diabetes and Thyroid Ctr of FW

Fort Worth, Texas, United States

Site Status

PlanIt Research, PLLC

Houston, Texas, United States

Site Status

Sun Research Institute

San Antonio, Texas, United States

Site Status

Simcare Medical Research, LLC

Sugar Land, Texas, United States

Site Status

Hillcrest Family Health Center

Waco, Texas, United States

Site Status

Capital Clin Res Ctr,LLC

Olympia, Washington, United States

Site Status

Medical center Medi City 21 OOD

Kyustendil, , Bulgaria

Site Status

MHAT Med Line Clinic

Plovdiv, , Bulgaria

Site Status

OCIPSOMCEMD ENDO MED-CONSULT - Dr. Nikolay Botushanov

Plovdiv, , Bulgaria

Site Status

ASOMCEM - Individual Practice - Dr. Antoanela Slavcheva

Rousse, , Bulgaria

Site Status

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

Sofia, , Bulgaria

Site Status

UMHAT Sofiamed EAD

Sofia, , Bulgaria

Site Status

InnoDiab Forschung GmbH

Essen, , Germany

Site Status

Wendisch/Dahl Hamburg (DZHW)

Hamburg, , Germany

Site Status

Milek, Hohenmölsen

Hohenmölsen, , Germany

Site Status

Institut für Diabetesforschung GmbH Münster - Dr. med. Rose

Münster, , Germany

Site Status

Praxis Dr. med. Wenzl-Bauer

Rehlingen-Siersburg, , Germany

Site Status

Zentrum für klinische Studien Alexander Segner

Saint Ingbert-Oberwürzbach, , Germany

Site Status

VvP Kliniken gGmbH Marienhospital Stuttgart - Innere Medizin I

Stuttgart, , Germany

Site Status

MZM Praxis Drs. Erlinger

Stuttgart, , Germany

Site Status

Hayashi Diabetes Clinic_Internal Medicine and Diabetes Medicine

Chigasaki-shi, Kanagawa, Japan, Japan

Site Status

Heiwadai Hospital_Internal Medicine

Miyazaki, Miyazaki, Japan

Site Status

Tokuyama clinic_Diabetic internal medicine

Chiba, , Japan

Site Status

Futata Tetsuhiro Clinic Meinohama_Internal medicine

Fukuoka-shi, Fukuoka, , Japan

Site Status

Naka Kinen Clinic_Internal medicine

Ibaraki, , Japan

Site Status

Yuri Ono Clinic

Sapporo-shi, Hokkaido, , Japan

Site Status

Oyama East Clinic_Internal Medicine

Tochigi, , Japan

Site Status

Juntendo University Hospital_Tokyo

Tokyo, , Japan

Site Status

Noritake Clinic

Ushiku-shi, Ibaraki, , Japan

Site Status

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

Lodz, , Poland

Site Status

NZOZ "DiabMed" Poradnia Diabetologiczna

Poznan, , Poland

Site Status

Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych I Administracji

Warsaw, , Poland

Site Status

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

Senhora Da Hora, Matosinhos, Matosinhos, Portugal

Site Status

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

Almada, , Portugal

Site Status

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

Coimbra, , Portugal

Site Status

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

Lisbon, , Portugal

Site Status

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

Porto, , Portugal

Site Status

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

Porto, , Portugal

Site Status

Hospital Luz Arrabida, S.A.

Vila Nova de Gaia, , Portugal

Site Status

Greenacres Hospital

Port Elizabeth, Eastern Cape, South Africa

Site Status

Medi-Clinic Bloemfontein

Bloemfontein, Free State, South Africa

Site Status

Hemant Makan

Johannesburg, Gauteng, South Africa

Site Status

Chris Hani Baragwanath Hospital

Johannesburg, Gauteng, South Africa

Site Status

Centre for Diabetes

Johannesburg, Gauteng, South Africa

Site Status

Dr A Amod

Durban, KwaZulu-Natal, South Africa

Site Status

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

Suwon, Gyeonggi-do, South Korea

Site Status

Seoul National University Bundang Hospital

Gyeonggi-do, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Kangbuk Samsung Hospital

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Nowon Eulji Medical Center, Eulji University

Seoul, , South Korea

Site Status

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

Dnipro, , Ukraine

Site Status

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

Kyiv, , Ukraine

Site Status

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

Kyiv, , Ukraine

Site Status

Ternopil Central District Hospital - Outpatient department

Ternopil, , Ukraine

Site Status

Countries

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United States Bulgaria Germany Japan Poland Portugal South Africa South Korea Ukraine

References

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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.

Reference Type RESULT
PMID: 36106652 (View on PubMed)

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.

Reference Type RESULT
PMID: 37148899 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40465144 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40186685 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39368488 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39344833 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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U1111-1247-4945

Identifier Type: OTHER

Identifier Source: secondary_id

2020-000454-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NN1436-4478

Identifier Type: -

Identifier Source: org_study_id

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