A Research Study to Compare Two Types of Insulin, a New Insulin, Insulin Icodec and an Available Insulin, Insulin Degludec, in People With Type 2 Diabetes Who Have Not Used Insulin Before (ONWARDS 3)

NCT ID: NCT04795531

Last Updated: 2024-12-04

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

588 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-24

Study Completion Date

2022-06-23

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 get their study medicine in an injection pen. Participants will get a pen for weekly injection and one for daily injection. One will be icodec or degludec and the other will be dummy medicine. The treatment participants get is decided by chance. Participants and the study staff will not know which active medicine they get.

The insulin is injected with a needle in a skin fold in the thigh. The study could last for about 8 months. Participants will have 13 clinic visits and 17 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.

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

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Once weekly insulin icodec + once daily placebo

Participants will get once daily and once weekly injections

Group Type EXPERIMENTAL

Insulin icodec

Intervention Type DRUG

You will get a pen for weekly injection and one for daily injection. One will be icodec 700 units/mL and the other will be placebo.

Subcutaneously (under the skin) injections

Placebo insulin degludec

Intervention Type DRUG

You will get a pen for weekly injection and one for daily injection. One will be icodec 700 units/mL and the other will be placebo.

Subcutaneously (under the skin) injections

Once weekly placebo and once daily insulin degludec

Participants will get once daily and once weekly injections

Group Type EXPERIMENTAL

Placebo insulin icodec

Intervention Type DRUG

You will get a pen for weekly injection and one for daily injection. One will be insulin degludec 100 units/mL and the other will be placebo.

Subcutaneously (under the skin) injections

Insulin degludec

Intervention Type DRUG

You will get a pen for weekly injection and one for daily injection. One will be degludec 100 units/mL and the other will be placebo.

Subcutaneously (under the skin) injections

Interventions

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Insulin icodec

You will get a pen for weekly injection and one for daily injection. One will be icodec 700 units/mL and the other will be placebo.

Subcutaneously (under the skin) injections

Intervention Type DRUG

Placebo insulin icodec

You will get a pen for weekly injection and one for daily injection. One will be insulin degludec 100 units/mL and the other will be placebo.

Subcutaneously (under the skin) injections

Intervention Type DRUG

Insulin degludec

You will get a pen for weekly injection and one for daily injection. One will be degludec 100 units/mL and the other will be placebo.

Subcutaneously (under the skin) injections

Intervention Type DRUG

Placebo insulin degludec

You will get a pen for weekly injection and one for daily injection. One will be icodec 700 units/mL and the other will be placebo.

Subcutaneously (under the skin) injections

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 (type 2 diabetes) greater than or equal to 180 days prior to the day of screening.
* HbA1c (glycated haemoglobin) from 7.0-11.0% (53.0-96.7 mmol/mol) both inclusive at screening confirmed by central laboratory analysis.
* Insulin naïve. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes.
* Stable daily dose(s) greater than or equal to 90 days prior to the day of screening of any of the following anti-diabetic drug(s) or combination regimen(s):

a.) Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose. b.) Any metformin combination formulations greater than or equal to 1500 mg or maximum tolerated or effective dose. c.) Any of the following oral anti-diabetic drug classes including combinations (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose).:Sulfonylureas - Meglitinides (glinides) - DPP-4 inhibitors - SGLT2 inhibitors - Thiazolidinediones - Alpha-glucosidase inhibitors - Oral combination products (for the allowed individual Oral Anti-diabetic Drugs (OADs)) - 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 (NYHA) Class IV at screening.
* Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids).
* Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
Minimum Eligible Age

18 Years

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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Lakeview Clinical Research, LLC

Guntersville, Alabama, United States

Site Status

American Clinical Trials

Buena Park, California, United States

Site Status

Headlands Research California, LLC

Escondido, California, United States

Site Status

Valley Research

Fresno, California, United States

Site Status

First Valley Medical Group

Lancaster, California, United States

Site Status

Est Cst Inst for Rsrch,Jksnvil

Jacksonville, Florida, United States

Site Status

Palm Harbor Medical Associates

Palm Harbor, Florida, United States

Site Status

Metabolic Research Institute Inc

West Palm Beach, Florida, United States

Site Status

Cedar-Crosse Research Center

Chicago, Illinois, United States

Site Status

Cotton-Oneill Diabetes and End

Topeka, Kansas, United States

Site Status

Arcturus Healthcare, PLC

Troy, Michigan, United States

Site Status

Southgate Medical Group, LLP

West Seneca, New York, United States

Site Status

Physician's East Endocrinology

Greenville, North Carolina, United States

Site Status

Accellacare

Wilmington, North Carolina, United States

Site Status

Diab & Endo Assoc of Stark Co

Canton, Ohio, United States

Site Status

Providence Health Partners Ctr

Dayton, Ohio, United States

Site Status

Prestige Clinical Research

Franklin, Ohio, United States

Site Status

Intend Research

Norman, Oklahoma, United States

Site Status

Hillcrest Clinical Research

Simpsonville, South Carolina, United States

Site Status

Velocity Clinical Res-Dallas

Dallas, Texas, United States

Site Status

UT Southwestern Med Cntr

Dallas, Texas, United States

Site Status

PrimeCare Medical Group

Houston, Texas, United States

Site Status

Texas Diab & Endo, P.A.

Round Rock, Texas, United States

Site Status

Clinical Trials of Texas, LLC

San Antonio, Texas, United States

Site Status

Chrysalis Clinical Research

St. George, Utah, United States

Site Status

Rainier Clin Res Ctr Inc

Renton, Washington, United States

Site Status

STAT Research

Buenos Aires, , Argentina

Site Status

Centro de Investigación Clínica

CABA, , Argentina

Site Status

Medical Center of Diabetes and Nutrition

CABA, , Argentina

Site Status

Instituto de Clínica Médica y Diabetes

Mendoza, , Argentina

Site Status

Universitätsklinik für Innere Medizin Graz

Graz, , Austria

Site Status

Universitätsklinik für Innere Medizin

Graz, , Austria

Site Status

Barmh. Brüder Linz, Konventspital

Linz, , Austria

Site Status

Gesundheitszentrum Hetzendorf

Vienna, , Austria

Site Status

Hanusch-Krankenhaus, Wien

Vienna, , Austria

Site Status

Quanta Diagnóstico Nuclear / Medicina Nuclear Alto da XV

Curitiba, Paraná, Brazil

Site Status

Centro de Diabetes Curitiba

Curitiba, Paraná, Brazil

Site Status

Núcleo de Pesquisa Clínica do Rio Grande do Sul Ltda.

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

CPQuali Pesquisa Clínica Ltda

São Paulo, São Paulo, Brazil

Site Status

Commonwealth Medical Clinic

Mount Pearl, Newfoundland and Labrador, Canada

Site Status

Eastern Health Authority

St. John's, Newfoundland and Labrador, Canada

Site Status

LMC Diabetes & Endocrinology (Barrie)

Barrie, Ontario, Canada

Site Status

LMC ClinRsrh Inc.Brampton

Brampton, Ontario, Canada

Site Status

LMC (Thornhill)

Concord, Ontario, Canada

Site Status

LMC Endo Ctr (Etobicoke) Ltd

Etobicoke, Ontario, Canada

Site Status

Western Univ. Cnt for Studies in Fam Med

London, Ontario, Canada

Site Status

LMC Research Inc. Ottawa

Nepean, Ontario, Canada

Site Status

Bluewater Clin Res Group,Inc

Sarnia, Ontario, Canada

Site Status

Centricity Research LMC

Toronto, Ontario, Canada

Site Status

Dr. Anil K Gupta Medicine Professional Corporation

Toronto, Ontario, Canada

Site Status

ViaCar Recherche Clinique Inc

Brossard, Quebec, Canada

Site Status

Clinique de Recherche Medpharmgene Inc.

Montreal, Quebec, Canada

Site Status

LMC Clin Rsrch Inc. (Montreal)

Saint-Laurent, Quebec, Canada

Site Status

Diex Recherche Victoriaville

Victoriaville, Quebec, Canada

Site Status

Chinese People's Liberation Army General Hospital

Beijing, Beijing Municipality, China

Site Status

Beijing Pinggu Hospital

Beijing, Beijing Municipality, China

Site Status

Chongqing University Three Gorges Hospital

Chongqing, Chongqing Municipality, China

Site Status

Cangzhou People's Hospital

Cangzhou, Hebei, China

Site Status

Harrison International Peace Hospital

Hengshui, Hebei, China

Site Status

Changzhou No.2 People's Hospital, Yanghu Branch

Changzhou, Jiangsu, China

Site Status

The Second Affiliated Hospital of Nanjing Medical University_Nanjing

Nanjing, Jiangsu, China

Site Status

Nanjing Jiangning Hospital

Nanjing, Jiangsu, China

Site Status

The Affiliated Hospital of Jiangsu University_Zhenjiang

Zhenjiang, Jiangsu, China

Site Status

Jinan Central Hospital

Ji'nan, Shandong, China

Site Status

Shanghai Tenth People's Hsopital, Tongji University

Shanghai, Shanghai Municipality, China

Site Status

Shanghai Fifth People's Hospital

Shanghai, Shanghai Municipality, China

Site Status

General Hospital of Tianjin Medical University

Tianjin, Tianjin Municipality, China

Site Status

Edumed Broumov

Broumov, , Czechia

Site Status

Diahelp - diabetologie

Pardubice, , Czechia

Site Status

DIALINE s.r.o.

Plzeň 3, , Czechia

Site Status

Diabet2 s.r.o.

Prague, , Czechia

Site Status

EUC Klinika Praha a.s.

Prague, , Czechia

Site Status

Fledip s.r.o.

Prague, , Czechia

Site Status

Aarhus Universitetshospital Diabetes og Hormonsygdomme

Aarhus N, , Denmark

Site Status

Sydvestjysk Sygehus Esbjerg

Esbjerg, , Denmark

Site Status

Steno Diabetes Center Cph_Steno Diabetes Center Cph

Hellerup, , Denmark

Site Status

Hvidovre Hospital Endokrinologisk forsk. afs. 159

Hvidovre, , Denmark

Site Status

Les Hopitaux de Chartres-Hopital Louis Pasteur

Le Coudray, , France

Site Status

Centre Hospitalier de Narbonne

Narbonne, , France

Site Status

Ap-Hp-Hopital Bichat-Claude Bernard-1

Paris, , France

Site Status

Centre Hospitalier Universitaire de Bordeaux-Hopital Haut Leveque-2

Pessac, , France

Site Status

Hospices Civils de Lyon-Hopital Lyon Sud-1

Pierre-Bénite, , France

Site Status

Centre Hospitalier Universitaire de Nantes-Hopital Nord Laennec-3

Saint-Herblain, , France

Site Status

Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil-2

Toulouse, , France

Site Status

Centre de Recherche Clinique Portes Du Sud

Vénissieux, , France

Site Status

Arechavaleta Granell María del Rosario

Guadalajara, Jalisco, Mexico

Site Status

Investigación Médica Sonora S.C.

Hermosillo, Sonora, Mexico

Site Status

Advanced Clinical Research LLC

Bayamón, , Puerto Rico

Site Status

Changhua Christian Hospital

Changhua, , Taiwan

Site Status

Chung Shan Medical University Hospital

Taichung, , Taiwan

Site Status

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status

Chi Mei Medical Center

Tainan City, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Countries

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United States Argentina Austria Brazil Canada China Czechia Denmark France Mexico Puerto Rico Taiwan

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, 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)

Li Y, Kar S, Li C, Liu M, Luan Z, Yuan G, Zhong X, Mu Y. Once-Weekly Insulin Icodec Versus Once-Daily Insulin Degludec in Insulin-Naive Chinese Participants with Type 2 Diabetes: A Post Hoc Analysis of ONWARDS 3. Diabetes Ther. 2025 Apr;16(4):685-699. doi: 10.1007/s13300-025-01701-2. Epub 2025 Feb 28.

Reference Type DERIVED
PMID: 40016570 (View on PubMed)

Lingvay I, Asong M, Desouza C, Gourdy P, Kar S, Vianna A, Vilsboll T, Vinther S, Mu Y. Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes: The ONWARDS 3 Randomized Clinical Trial. JAMA. 2023 Jul 18;330(3):228-237. doi: 10.1001/jama.2023.11313.

Reference Type DERIVED
PMID: 37354562 (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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U1111-1247-5218

Identifier Type: OTHER

Identifier Source: secondary_id

2020-000472-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NN1436-4479

Identifier Type: -

Identifier Source: org_study_id