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)

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 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.

Official Title
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A 26-week Double Blinded, Multiregional, Trial Comparing the Effect and Safety of Once Weekly Insulin Icodec and Once Daily Insulin Degludec 100 Units/mL, Both in Combination With Non-insulin Anti-diabetic Drugs, in Insulin naïve Subjects With Type 2 Diabetes.

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin icodec
* Drug: Placebo insulin icodec
* Drug: Insulin degludec
* Drug: Placebo insulin degludec


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 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.

Ages Eligible for Study
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Minimum Age: 18 Years

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Once weekly insulin icodec + once daily placebo<br>Participants will get once daily and once weekly injections | Drug: Insulin icodec<br>* 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<br>Drug: Placebo insulin degludec<br>* 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<br>|
| Experimental: Once weekly placebo and once daily insulin degludec<br>Participants will get once daily and once weekly injections | Drug: Placebo insulin icodec<br>* 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<br>Drug: Insulin degludec<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c (glycated haemoglobin) | %-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) | mmol/L | From baseline week 0 (V2) 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) | 
| Number of severe hypoglycaemic episodes (level 3) | Number of episodes | From baseline week 0 (V2) to week 26 (V28) | 
| 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 26 (V28) | 
| 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 26 (V28) | 
| Change in body weight | Kg | From baseline week 0 (V2) to week 26 (V28) | 
| Mean weekly insulin dose | U | From week 24 (P26) to week 26 (V28) |