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)

Study Overview
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Brief Summary
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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.

Official Title
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A 26-week Trial Comparing the Effect and Safety of Once Weekly Insulin Icodec and Once Daily Insulin Glargine 100 Units/mL, Both in Combination With Bolus Insulin With or Without Non-insulin Anti-diabetic Drugs, in Subjects With Type 2 Diabetes on a Basal-bolus Regimen

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin icodec
* Drug: Insulin glargine
* Drug: Insulin aspart


Participation Criteria
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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 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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: insulin icodec + insulin aspart<br>Participants will get once weekly injections in combination with 2-4 times daily injections of insulin aspart | Drug: Insulin icodec<br>* Participants will receive subcutaneous (s.c.) injections of insulin icodec once weekly for 26 weeks<br>Drug: Insulin aspart<br>* Participants will receive subcutaneous (s.c.) injections of insulin aspart 2-4 times daily for 26 weeks<br>|
| Active Comparator: Insulin glargine + insulin aspart<br>Participants will get once daily injections in combination with 2-4 times daily injections of insulin aspart | Drug: Insulin glargine<br>* Participants will receive subcutaneous (s.c.) injections of insulin glargine once daily for 26 weeks<br>Drug: Insulin aspart<br>* Participants will receive subcutaneous (s.c.) injections of insulin aspart 2-4 times daily for 26 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycated haemoglobin (HbA1c) | Measured in %-point | From baseline week 0 (V2) to week 26 (V28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fasting plasma glucose (FPG) | Measured in mmol/L | From baseline week 0 (V2) to week 26 (V28) | 
| Time in target-range 3.9-10.0 mmol/L (70-180 mg/dL) (using continuous glucose monitoring (CGM) system, Dexcom G6) | Measured in % of readings | From week 22 (V24) to week 26 (V28) | 
| Number of severe hypoglycaemic episodes (level 3) | Number of episodes | From baseline week 0 (V2) to week 31 (V30) | 
| Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter) | Number of episodes | From baseline week 0 (V2) to week 31 (V30) | 
| Number of clinically significant hypoglycaemic episodes (level 2) (below 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 31 (V30) | 
| Time spent below 3.0 mmol/L (54 mg/dL) (using continuous glucose monitoring (CGM) system, Dexcom G6 ) | Measured in % of readings | From week 22 (V24) to week 26 (V28) | 
| Time spent above 10 mmol/L (180 mg/dL) (using continuous glucose monitoring (CGM) system, Dexcom G6) | Measured in % of readings | From week 22 (V24) to week 26 (V28) | 
| Mean weekly insulin dose | Measured in U | From week 24 (V26) to week 26 (V28) | 
| Change in body weight | Measured in kg | From baseline week 0 (V2) to week 26 (V28) |