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)

NCT04795531 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: NN1436-4479U1111-1247-52182020-000472-37
• Study Type: interventional
• Target: 588
• Locations: 12 countries
• Sites: 93

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 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.

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 is evaluated based on the in-trial observation period. The in-trial 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 (9)

• Change in Fasting Plasma Glucose (FPG)

  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 Milligrams Per Deciliter [mg/dL]), Confirmed by Blood Glucose [BG] Meter)

  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)

  From baseline (week 0) to week 31

• Number of Severe Hypoglycaemic Episodes (Level 3)

  From baseline (week 0) to week 26

Study Arms (2)

Once weekly insulin icodec + once daily placebo

EXPERIMENTAL

Participants will get once daily and once weekly injections

Drug: Insulin icodec; Drug: Placebo insulin degludec

Once weekly placebo and once daily insulin degludec

EXPERIMENTAL

Participants will get once daily and once weekly injections

Drug: Placebo insulin icodec; Drug: Insulin degludec

Interventions

Insulin icodec 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 insulin icodec + once daily placebo

Placebo insulin icodec 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

Once weekly placebo and once daily insulin degludec

Insulin degludec 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

Once weekly placebo and once daily insulin degludec

Placebo insulin degludec 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 insulin icodec + once daily placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: 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 (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.

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 (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.

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (93)

Lakeview Clinical Research, LLC

Guntersville, Alabama, 35976, United States

Location

American Clinical Trials

Buena Park, California, 90620, United States

Location

Headlands Research California, LLC

Escondido, California, 92025, United States

Location

Valley Research

Fresno, California, 93720, United States

Location

First Valley Medical Group

Lancaster, California, 93534, United States

Location

Est Cst Inst for Rsrch,Jksnvil

Jacksonville, Florida, 32216, United States

Location

Palm Harbor Medical Associates

Palm Harbor, Florida, 34684-3609, United States

Location

Metabolic Research Institute Inc

West Palm Beach, Florida, 33401, United States

Location

Cedar-Crosse Research Center

Chicago, Illinois, 60607, United States

Location

Cotton-Oneill Diabetes and End

Topeka, Kansas, 66606-2806, United States

Location

Arcturus Healthcare, PLC

Troy, Michigan, 48098, United States

Location

Southgate Medical Group, LLP

West Seneca, New York, 14224, United States

Location

Physician's East Endocrinology

Greenville, North Carolina, 27834, United States

Location

Accellacare

Wilmington, North Carolina, 28401, United States

Location

Diab & Endo Assoc of Stark Co

Canton, Ohio, 44718, United States

Location

Providence Health Partners Ctr

Dayton, Ohio, 45439, United States

Location

Prestige Clinical Research

Franklin, Ohio, 45005, United States

Location

Intend Research

Norman, Oklahoma, 73069, United States

Location

Hillcrest Clinical Research

Simpsonville, South Carolina, 29681-1538, United States

Location

Velocity Clinical Res-Dallas

Dallas, Texas, 75230, United States

Location

UT Southwestern Med Cntr

Dallas, Texas, 75390-9302, United States

Location

PrimeCare Medical Group

Houston, Texas, 77024, United States

Location

Texas Diab & Endo, P.A.

Round Rock, Texas, 78681, United States

Location

Clinical Trials of Texas, LLC

San Antonio, Texas, 78229, United States

Location

Chrysalis Clinical Research

St. George, Utah, 84790, United States

Location

Rainier Clin Res Ctr Inc

Renton, Washington, 98057, United States

Location

STAT Research

Buenos Aires, C1023AAB, Argentina

Location

Centro de Investigación Clínica

CABA, C1060ABA, Argentina

Location

Medical Center of Diabetes and Nutrition

CABA, C1440AAD, Argentina

Location

Instituto de Clínica Médica y Diabetes

Mendoza, 5500, Argentina

Location

Universitätsklinik für Innere Medizin Graz

Graz, 8036, Austria

Location

Universitätsklinik für Innere Medizin

Graz, 8036, Austria

Location

Barmh. Brüder Linz, Konventspital

Linz, 4021, Austria

Location

Gesundheitszentrum Hetzendorf

Vienna, 1120, Austria

Location

Hanusch-Krankenhaus, Wien

Vienna, 1140, Austria

Location

Quanta Diagnóstico Nuclear / Medicina Nuclear Alto da XV

Curitiba, Paraná, 80045-170, Brazil

Location

Centro de Diabetes Curitiba

Curitiba, Paraná, 80810-040, Brazil

Location

Núcleo de Pesquisa Clínica do Rio Grande do Sul Ltda.

Porto Alegre, Rio Grande do Sul, 90430-001, Brazil

Location

CPQuali Pesquisa Clínica Ltda

São Paulo, São Paulo, 01228-000, Brazil

Location

Commonwealth Medical Clinic

Mount Pearl, Newfoundland and Labrador, A1N 1W7, Canada

Location

Eastern Health Authority

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

LMC Diabetes & Endocrinology (Barrie)

Barrie, Ontario, L4N 7L3, Canada

Location

LMC ClinRsrh Inc.Brampton

Brampton, Ontario, L6S 0C6, Canada

Location

LMC (Thornhill)

Concord, Ontario, L4K 4M2, Canada

Location

LMC Endo Ctr (Etobicoke) Ltd

Etobicoke, Ontario, M9R 4E1, Canada

Location

Western Univ. Cnt for Studies in Fam Med

London, Ontario, N6G 2M1, Canada

Location

LMC Research Inc. Ottawa

Nepean, Ontario, K2J 0V2, Canada

Location

Bluewater Clin Res Group,Inc

Sarnia, Ontario, N7T 4X3, Canada

Location

Centricity Research LMC

Toronto, Ontario, M4G 3E8, Canada

Location

Dr. Anil K Gupta Medicine Professional Corporation

Toronto, Ontario, M9V 4B4, Canada

Location

ViaCar Recherche Clinique Inc

Brossard, Quebec, J4Z 2K9, Canada

Location

Clinique de Recherche Medpharmgene Inc.

Montreal, Quebec, H1Y 3L1, Canada

Location

LMC Clin Rsrch Inc. (Montreal)

Saint-Laurent, Quebec, H4T 1Z9, Canada

Location

Diex Recherche Victoriaville

Victoriaville, Quebec, G6P 6P6, Canada

Location

Chinese People's Liberation Army General Hospital

Beijing, Beijing Municipality, 100853, China

Location

Beijing Pinggu Hospital

Beijing, Beijing Municipality, 101200, China

Location

Chongqing University Three Gorges Hospital

Chongqing, Chongqing Municipality, 404000, China

Location

Cangzhou People's Hospital

Cangzhou, Hebei, 061000, China

Location

Harrison International Peace Hospital

Hengshui, Hebei, 053000, China

Location

Changzhou No.2 People's Hospital, Yanghu Branch

Changzhou, Jiangsu, 213003, China

Location

The Second Affiliated Hospital of Nanjing Medical University_Nanjing

Nanjing, Jiangsu, 210011, China

Location

Nanjing Jiangning Hospital

Nanjing, Jiangsu, 211199, China

Location

The Affiliated Hospital of Jiangsu University_Zhenjiang

Zhenjiang, Jiangsu, 212001, China

Location

Jinan Central Hospital

Ji'nan, Shandong, 250013, China

Location

Shanghai Tenth People's Hsopital, Tongji University

Shanghai, Shanghai Municipality, 200072, China

Location

Shanghai Fifth People's Hospital

Shanghai, Shanghai Municipality, 200240, China

Location

General Hospital of Tianjin Medical University

Tianjin, Tianjin Municipality, 300052, China

Location

Edumed Broumov

Broumov, 550 01, Czechia

Location

Diahelp - diabetologie

Pardubice, 530 02, Czechia

Location

DIALINE s.r.o.

Plzeň 3, 301 00, Czechia

Location

Diabet2 s.r.o.

Prague, 110 00, Czechia

Location

EUC Klinika Praha a.s.

Prague, 150 00, Czechia

Location

Fledip s.r.o.

Prague, 160 00, Czechia

Location

Aarhus Universitetshospital Diabetes og Hormonsygdomme

Aarhus N, 8200, Denmark

Location

Sydvestjysk Sygehus Esbjerg

Esbjerg, 6700, Denmark

Location

Steno Diabetes Center Cph_Steno Diabetes Center Cph

Hellerup, 2900, Denmark

Location

Hvidovre Hospital Endokrinologisk forsk. afs. 159

Hvidovre, 2650, Denmark

Location

Les Hopitaux de Chartres-Hopital Louis Pasteur

Le Coudray, 28630, France

Location

Centre Hospitalier de Narbonne

Narbonne, 11100, France

Location

Ap-Hp-Hopital Bichat-Claude Bernard-1

Paris, 75877, France

Location

Centre Hospitalier Universitaire de Bordeaux-Hopital Haut Leveque-2

Pessac, 33600, France

Location

Hospices Civils de Lyon-Hopital Lyon Sud-1

Pierre-Bénite, 69310, France

Location

Centre Hospitalier Universitaire de Nantes-Hopital Nord Laennec-3

Saint-Herblain, 44800, France

Location

Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil-2

Toulouse, 31054, France

Location

Centre de Recherche Clinique Portes Du Sud

Vénissieux, 69200, France

Location

Arechavaleta Granell María del Rosario

Guadalajara, Jalisco, 44650, Mexico

Location

Investigación Médica Sonora S.C.

Hermosillo, Sonora, 83280, Mexico

Location

Advanced Clinical Research LLC

Bayamón, 00959, Puerto Rico

Location

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

Chung Shan Medical University Hospital

Taichung, 402, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 407, Taiwan

Location

Chi Mei Medical Center

Tainan, 710, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Related Publications (5)

• 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, 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

• 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.

  PMID: 40016570 DERIVED

• 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.

  PMID: 37354562 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

insulin icodec; insulin degludec

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2021
• First Posted: March 12, 2021
• Study Start: March 24, 2021
• Primary Completion: June 23, 2022
• Study Completion: June 23, 2022
• Last Updated: December 4, 2024
• Results First Posted: December 4, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

PR (1); CA (15); DK (4); CN (13); FR (8); TW (5); AR (4); AU (5); ME (2); US (26); CZ (6); BR (4)