A Research Study to Compare Two Types of Insulin, a New Weekly Insulin, Insulin Icodec and an Available Daily Insulin, Insulin Glargine, Both in Combination With Mealtime Insulin, in People With Type 2 Diabetes Who Use Daily Insulin and Mealtime Insulin (ONWARDS 4)

Phase 3

Completed

Conditions: Diabetes Mellitus, Type 2

Interventions: Drug: Insulin glargine
Drug: Insulin icodec
Drug: Insulin aspart

Registration Number: NCT04880850

Lead Sponsor: Novo Nordisk A/S

Brief Summary: 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 will get is decided by chance. Participants will also get a mealtime insulin.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: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 582

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) greater than or equal to 180 days prior to the day of screening.
Glycated haemoglobin (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 basal insulin (neutral protamine hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL) and 2-4 daily injections of bolus insulin analog (insulin aspart, faster acting insulin aspart, insulin lispro, insulin glulisine) 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
insulin icodec + insulin aspart	Insulin aspart	Participants will get once weekly injections in combination with 2-4 times daily injections of insulin aspart
Insulin glargine + insulin aspart	Insulin glargine	Participants will get once daily injections in combination with 2-4 times daily injections of insulin aspart
Insulin glargine + insulin aspart	Insulin aspart	Participants will get once daily injections in combination with 2-4 times daily injections of insulin aspart
insulin icodec + insulin aspart	Insulin icodec	Participants will get once weekly injections in combination with 2-4 times daily injections of insulin aspart

Primary Outcome Measures

Name	Time	Method
Change in Glycated Haemoglobin (HbA1c)	Baseline (week 0), Week 26	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.

Secondary Outcome Measures

Name	Time	Method
Change in Fasting Plasma Glucose (FPG)	Baseline (week 0), Week 26	Change in FPG 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.
Percentage of Time in Target-range 3.9-10.0 mmol/L (70-180 mg/dL) Using Continuous Glucose Monitoring (CGM) System	From week 22 to week 26	Percentage of time in target-range 3.9-10.0 mmol/L (70-180 milligrams per deciliter \[mg/dL\]) using continuous glucose monitoring (CGM) system from week 22 to week 26 is presented. Time in target range is defined as 100 times the number of recorded measurements in glycaemic target range 3.9-10.0 mmol/L (70-180 mg/dL), both inclusive, divided by the total number of recorded measurements. 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.
Number of Severe Hypoglycaemic Episodes (Level 3)	From baseline (week 0) to week 31	Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. The outcome data was evaluated based on the on-treatment observation period. The on-treatment observation period started at the date of first dose of trial product as recorded on the electronic case report form (eCRF), and ended at the first date of any of the following: The end of trial visit, the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of the dosing interval for both treatment arms) and the end-date for the in-trial observation period.
Percentage of Time Spent Above 10 mmol/L (180 mg/dL) Using Continuous Glucose Monitoring (CGM) System	From week 22 to week 26	Percentage of time spent \> 10 mmol/L (180 mg/dL) using CGM system from week 22 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.
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL) Confirmed by Blood Glucose (BG) Meter)	From baseline (week 0) to week 31	Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (\<) 3.0 mmol/L (54 mg/dL). The outcome data was evaluated based on the on-treatment observation period. The on-treatment observation period started at the date of first dose of trial product as recorded on the electronic case report form (eCRF), and ended at the first date of any of the following: The end of trial visit, the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of the dosing interval for both treatment arms) and the end-date for the in-trial observation period.
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	Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (\<) 3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. The outcome data was evaluated based on the in-trial observation period. The on-treatment observation period started at the date of first dose of trial product as recorded on the electronic case report form (eCRF), and ended at the first date of any of the following: The end of trial visit, the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of the dosing interval for both treatment arms) and the end-date for the in-trial observation period.
Percentage of Time Spent Below 3.0 mmol/L (54 mg/dL) Using Continuous Glucose Monitoring (CGM) System	From week 22 to week 26	Percentage of time spent less than (\<) 3.0 mmol/L (54 mg/dL) using CGM system from week 22 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.
Mean Weekly Insulin Dose	From week 24 to week 26	Estimated mean weekly insulin dose during the last 2 weeks of treatment (from week 24 to week 26) is presented. The outcome data was evaluated based on the on-treatment observation period. The on-treatment observation period started at the date of first dose of trial product as recorded on the electronic case report form (eCRF), and ended at the first date of any of the following: The end of trial visit, the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of the dosing interval for both treatment arms) and the end-date for the in-trial observation period.
Change in Body Weight	Baseline (week 0), Week 26	Change in body weight 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.

Trial Locations

Locations (81): John Muir Physicians Network
🇺🇸
Concord, California, United States
Valley Research
🇺🇸
Fresno, California, United States
Valley Clinical Trials, Inc.
🇺🇸
Northridge, California, United States
Clinical Trials Research_Sacramento_0
🇺🇸
Sacramento, California, United States
Diabetes Research Center
🇺🇸
Tustin, California, United States
Coastal Metabolic Research Center
🇺🇸
Ventura, California, United States
Diablo Clinical Research, Inc.
🇺🇸
Walnut Creek, California, United States
MedStar Diabetes Institute
🇺🇸
Washington, District of Columbia, United States
Metabolic Research Institute Inc
🇺🇸
West Palm Beach, Florida, United States
Physicians Research Assoc. LLC
🇺🇸
Lawrenceville, Georgia, United States
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John Muir Physicians Network
🇺🇸Concord, California, United States