A Research Study to Compare Two Types of Insulin, a New Insulin, Insulin Icodec and an Available Insulin, Insulin Glargine, in People With Type 2 Diabetes Who Have Not Used Insulin Before (ONWARDS 1)

A 78-week Trial Comparing the Effect and Safety of Once Weekly Insulin Icodec and Once Daily Insulin Glargine 100 Units/mL, Both in Combination With Non-insulin Anti-diabetic Treatment, in Insulin naïve Subjects With Type 2 Diabetes

This study compares insulin icodec (a new insulin taken once a week) to insulin glargine (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 glargine 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 glargine 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 1 ½ years. Participants will have 37 clinic visits and 26 phone calls with the study doctor. At 11 clinic visits participant will have blood samples taken. At 8 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 the blood sugar all the time in 5 periods of about one month during the study (about 5 months in total). Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Insulin icodec; Drug: Insulin glargine

• Study Type: Interventional
• Enrollment (Actual): 984
• Phase: Phase 3

Contacts and Locations

Study Locations

• Croatia
  • Karlovac, Croatia, 47000
    • Novo Nordisk Investigational Site
  • Rijeka, Croatia, 51000
    • Novo Nordisk Investigational Site
  • Varazdin, Croatia, 42 000
    • Novo Nordisk Investigational Site
  • Osječko - Baranjska Županija
    • Osijek, Osječko - Baranjska Županija, Croatia, 31000
      • Novo Nordisk Investigational Site
• India
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500072
      • Novo Nordisk Investigational Site
  • Haryana
    • Rohtak, Haryana, India, 124001
      • Novo Nordisk Investigational Site
  • Madhya Pradesh
    • Indore, Madhya Pradesh, India, 452010
      • Novo Nordisk Investigational Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400008
      • Novo Nordisk Investigational Site
    • Pune, Maharashtra, India, 411021
      • Novo Nordisk Investigational Site
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600086
      • Novo Nordisk Investigational Site
    • Vellore, Tamil Nadu, India, 632004
      • Novo Nordisk Investigational Site
  • Telengana
    • Hyderabad, Telengana, India, 500003
      • Novo Nordisk Investigational Site
    • Hyderbad, Telengana, India, 500 012
      • Novo Nordisk Investigational Site
• Israel
  • Holon, Israel, 58100
    • Novo Nordisk Investigational Site
  • Jerusalem, Israel, 91120
    • Novo Nordisk Investigational Site
  • Kfar Saba, Israel, 44281
    • Novo Nordisk Investigational Site
  • Petach Tikva, Israel, 49100
    • Novo Nordisk Investigational Site
  • Rehovot, Israel, 76100
    • Novo Nordisk Investigational Site
• Italy
  • Bergamo, Italy, 24127
    • Novo Nordisk Investigational Site
  • Catanzaro, Italy, 88100
    • Novo Nordisk Investigational Site
  • Milano, Italy, 20122
    • Novo Nordisk Investigational Site
  • Palermo, Italy, 90127
    • Novo Nordisk Investigational Site
  • RM
    • Roma, RM, Italy, 00161
      • Novo Nordisk Investigational Site
• Japan
  • Bunkyo-ku, Tokyo, Japan, 113-8655
    • Novo Nordisk Investigational Site
  • Chiba, Japan, 261-0004
    • Novo Nordisk Investigational Site
  • Fukuoka-shi, Fukuoka, Japan, 819-0006
    • Novo Nordisk Investigational Site
  • Ibaraki, Japan, 311-0113
    • Novo Nordisk Investigational Site
  • Kitakyusyu-shi, Fukuoka, Japan, 800-0222
    • Novo Nordisk Investigational Site
  • Minato-ku, Tokyo, Japan, 105-8470
    • Novo Nordisk Investigational Site
  • Miyagi, Japan, 983-0039
    • Novo Nordisk Investigational Site
  • Osaka, Japan, 569-1045
    • Novo Nordisk Investigational Site
  • Saitama, Japan, 336-0967
    • Novo Nordisk Investigational Site
  • Shimotsuke-shi, Tochigi, Japan, 329-0433
    • Novo Nordisk Investigational Site
  • Tochigi, Japan, 323-0022
    • Novo Nordisk Investigational Site
  • Ushiku-shi, Ibaraki, Japan, 300-1207
    • Novo Nordisk Investigational Site
  • Kanagawa, Japan
    • Chigasaki-shi, Kanagawa, Kanagawa, Japan, Japan, 253-0044
      • Novo Nordisk Investigational Site
  • Miyazaki, Japan
    • Miyazaki-shi, Miyazaki, Japan, Japan, 880-0034
      • Novo Nordisk Investigational Site
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44600
      • Novo Nordisk Investigational Site
  • México, D.F.
    • Mexico City, México, D.F., Mexico, 06700
      • Novo Nordisk Investigational Site
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Novo Nordisk Investigational Site
  • Sonora
    • Hermosillo, Sonora, Mexico, 83280
      • Novo Nordisk Investigational Site
• Poland
  • Gorzow Wielkopolski, Poland, 66-400
    • Novo Nordisk Investigational Site
  • Radom, Poland, 26-600
    • Novo Nordisk Investigational Site
  • Wierzchoslawice, Poland, 33-122
    • Novo Nordisk Investigational Site
  • Zabrze, Poland, 41-800
    • Novo Nordisk Investigational Site
  • Lubelski
    • Lublin, Lubelski, Poland, 20-538
      • Novo Nordisk Investigational Site
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-044
      • Novo Nordisk Investigational Site
  • Mazowieckie
    • Warsaw, Mazowieckie, Poland, 00-710
      • Novo Nordisk Investigational Site
  • Podlaskie
    • Bialystok, Podlaskie, Poland, 15-435
      • Novo Nordisk Investigational Site
• Puerto Rico
  • Bayamon, Puerto Rico, 00961
    • Novo Nordisk Investigational Site
  • Manati, Puerto Rico, 00674
    • Novo Nordisk Investigational Site
• Russian Federation
  • Kemerovo, Russian Federation, 650066
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 117292
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 119435
    • Novo Nordisk Investigational Site
  • Novosibirsk, Russian Federation, 630099
    • Novo Nordisk Investigational Site
  • Novosibirsk, Russian Federation, 630117
    • Novo Nordisk Investigational Site
  • Penza, Russian Federation, 440052
    • Novo Nordisk Investigational Site
  • Saint Petersburg, Russian Federation, 194291
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 194156
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 194356
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 197110
    • Novo Nordisk Investigational Site
  • Saratov, Russian Federation, 410039
    • Novo Nordisk Investigational Site
  • Tomsk, Russian Federation, 634050
    • Novo Nordisk Investigational Site
  • Voronezh, Russian Federation, 394018
    • Novo Nordisk Investigational Site
  • Yoshkar-Ola, Russian Federation, 424004
    • Novo Nordisk Investigational Site
• Slovakia
  • Bratislava, Slovakia, 84102
    • Novo Nordisk Investigational Site
  • Bratislava, Slovakia, 851 01
    • Novo Nordisk Investigational Site
  • Malacky, Slovakia, 901 01
    • Novo Nordisk Investigational Site
  • Moldava nad Bodvou, Slovakia, 045 01
    • Novo Nordisk Investigational Site
  • Trebisov, Slovakia, 07501
    • Novo Nordisk Investigational Site
  • Slovak Republic
    • Sahy, Slovak Republic, Slovakia, 93601
      • Novo Nordisk Investigational Site
• Spain
  • La Coruña, Spain, 15006
    • Novo Nordisk Investigational Site
  • La Roca del Vallés, Spain, 08430
    • Novo Nordisk Investigational Site
  • Madrid, Spain, 28006
    • Novo Nordisk Investigational Site
  • Madrid, Spain, 28020
    • Novo Nordisk Investigational Site
  • Pozuelo de Alarcon, Spain, 28223
    • Novo Nordisk Investigational Site
• United Kingdom
  • Blackpool, United Kingdom, FY3 7EN
    • Novo Nordisk Investigational Site
  • Bollington, United Kingdom, SK10 5JH
    • Novo Nordisk Investigational Site
  • Bradford-on-Avon, United Kingdom, BA15 1DQ
    • Novo Nordisk Investigational Site
  • Bristol, United Kingdom, BS10 5NB
    • Novo Nordisk Investigational Site
  • Cambridge, United Kingdom, CB2 0QQ
    • Novo Nordisk Investigational Site
  • Dorset, United Kingdom, BH16 5PW
    • Novo Nordisk Investigational Site
  • Edinburgh, United Kingdom, EH4 2XU
    • Novo Nordisk Investigational Site
  • Hinckley, United Kingdom, LE10 2SE
    • Novo Nordisk Investigational Site
  • Soham, United Kingdom, CB7 5JD
    • Novo Nordisk Investigational Site
  • Swansea, United Kingdom, SA2 8PP
    • Novo Nordisk Investigational Site
  • Truro, United Kingdom, TR1 3LJ
    • Novo Nordisk Investigational Site
  • Wellingborough, United Kingdom, NN8 4RW
    • Novo Nordisk Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Novo Nordisk Investigational Site
    • Guntersville, Alabama, United States, 35976
      • Novo Nordisk Investigational Site
  • California
    • Buena Park, California, United States, 90620
      • Novo Nordisk Investigational Site
    • Fresno, California, United States, 93720
      • Novo Nordisk Investigational Site
    • Lancaster, California, United States, 93534
      • Novo Nordisk Investigational Site
    • Palm Springs, California, United States, 92262
      • Novo Nordisk Investigational Site
    • Ventura, California, United States, 93003
      • Novo Nordisk Investigational Site
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Novo Nordisk Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Novo Nordisk Investigational Site
    • New Port Richey, Florida, United States, 34652
      • Novo Nordisk Investigational Site
    • Orlando, Florida, United States, 32825
      • Novo Nordisk Investigational Site
    • Palm Harbor, Florida, United States, 34684-3609
      • Novo Nordisk Investigational Site
    • West Palm Beach, Florida, United States, 33401
      • Novo Nordisk Investigational Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Novo Nordisk Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Novo Nordisk Investigational Site
    • Gurnee, Illinois, United States, 60031
      • Novo Nordisk Investigational Site
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Novo Nordisk Investigational Site
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Novo Nordisk Investigational Site
  • Kentucky
    • Paducah, Kentucky, United States, 42001
      • Novo Nordisk Investigational Site
  • Maryland
    • Hyattsville, Maryland, United States, 20782
      • Novo Nordisk Investigational Site
    • Rockville, Maryland, United States, 20852
      • Novo Nordisk Investigational Site
  • Michigan
    • Troy, Michigan, United States, 48098
      • Novo Nordisk Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198-3020
      • Novo Nordisk Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Novo Nordisk Investigational Site
  • New York
    • Brooklyn, New York, United States, 11215
      • Novo Nordisk Investigational Site
    • West Seneca, New York, United States, 14224
      • Novo Nordisk Investigational Site
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Novo Nordisk Investigational Site
    • Raleigh, North Carolina, United States, 27609
      • Novo Nordisk Investigational Site
    • Wilmington, North Carolina, United States, 28401
      • Novo Nordisk Investigational Site
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Novo Nordisk Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • Novo Nordisk Investigational Site
    • Dayton, Ohio, United States, 45439
      • Novo Nordisk Investigational Site
    • Franklin, Ohio, United States, 45005
      • Novo Nordisk Investigational Site
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Novo Nordisk Investigational Site
  • South Carolina
    • Murrells Inlet, South Carolina, United States, 29576
      • Novo Nordisk Investigational Site
    • Simpsonville, South Carolina, United States, 29681-1538
      • Novo Nordisk Investigational Site
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Novo Nordisk Investigational Site
  • Texas
    • Austin, Texas, United States, 78731
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75230
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75390-9302
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77024
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77074
      • Novo Nordisk Investigational Site
    • Lampasas, Texas, United States, 76550
      • Novo Nordisk Investigational Site
    • Live Oak, Texas, United States, 78233
      • Novo Nordisk Investigational Site
    • Round Rock, Texas, United States, 78681
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78229
      • Novo Nordisk Investigational Site
    • Sugar Land, Texas, United States, 77478
      • Novo Nordisk Investigational Site
  • Utah
    • Saint George, Utah, United States, 84790
      • Novo Nordisk Investigational Site
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Novo Nordisk Investigational Site
  • Washington
    • Renton, Washington, United States, 98057
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female aged above or equal to 18 years at the time of signing informed consent.
• Diagnosed with type 2 diabetes mellitus (T2D) 180 days or more prior to the day of screening.
• HbA1c 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) 90 days or more prior to the day of screening of any of the following anti-diabetic drug(s) or combination regimen(s): a. Any metformin formulations at least or greater than 1500 mg or maximum tolerated or effective dose. b. Any metformin combination formulations equal to or above 1500 mg or maximum tolerated or effective dose. c. Any of the following oral anti-diabetic drug classes including combinations ((equal to or above half of the maximum approved dose according to local label or maximum tolerated or effective dose): Sulfonylureas, Meglitinides (glinides), dipeptidyl peptidase-4 (DPP-4) inhibitors, Sodium-glucose co-transporter-2 (SGLT2) inhibitors, Thiazolidinediones, Alpha-glucosidase inhibitors, Oral combination products (for the allowed individual oral anti-diabetic drugs), Oral or injectable glucagon-like peptide 1 (GLP-1) receptor agonists
• Body mass index (BMI) equal to or below 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin icodec; Insulin icodec + non-insulin anti-diabetic drugs. The pre-trial non-insulin anti-diabetic background medication should be maintained at the stable, pre-trial dose and at the same frequency during the entire treatment period	Drug: Insulin icodec; Participants will receive subcutaneous (s.c.) injections of insulin icodec once weekly for 78 weeks.
Active Comparator: Insulin glargine; Insulin glargine + non-insulin anti-diabetic drugs. The pre-trial non-insulin anti-diabetic background medication should be maintained at the stable, pre-trial dose and at the same frequency during the entire treatment period	Drug: Insulin glargine; Participants will receive subcutaneous (s.c.) injections of insulin glargine once daily for 78 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c	%-point	From baseline week 0 (V2) to week 52 (V46)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in target range 3.9-10.0 mmol/L (70-180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6	% of readings	From week 48 (V42) to week 52 (V46)
Change in fasting plasma glucose (FPG)	mmol/L	From baseline week 0 (V2) to week 52 (V46)
Number of severe hypoglycaemic episodes (level 3)	Number of episodes	From baseline week 0 (V2) to week 52 (V46)
Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL) confirmed by BG meter)	Number of episodes	From baseline week 0 (V2) to week 52 (V46)
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 episodes	From baseline week 0 (V2) to week 52 (V46)
Number of severe hypoglycaemic episodes (level 3)	Number of episodes	From baseline week 0 (V2) to week 83 (V63)
Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL) confirmed by BG meter)	Number of episodes	From baseline week 0 (V2) to week 83 (V63)
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 episodes	From baseline week 0 (V2) to week 83 (V63)
Mean weekly insulin dose	U	From week 50 (V44) to week 52 (V46)
Change in body weight	kg	From baseline week 0 (V2) to week 52 (V46)
Time spent < 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6	% of readings	From week 48 (V42) to week 52 (V46)
Time spent > 10 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6	% of readings	From week 48 (V42) to week 52 (V46)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (1452), Novo Nordisk A/S

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2020
• Primary Completion (Actual): May 29, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: July 6, 2020
• First Submitted That Met QC Criteria: July 6, 2020
• First Posted (Actual): July 8, 2020

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 3, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine
• Other Study ID Numbers: NN1436-4477; U1111-1247-3878 (Other Identifier: World Health Organization (WHO)); 2020-000442-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No