A Trial Comparing Efficacy and Safety of Insulin Degludec and Insulin Glargine in Insulin naïve Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial was conducted in Africa, Asia, Europe, North and South America. The aim of the trial was to compare efficacy and safety of insulin degludec and insulin glargine in insulin naïve subjects with type 2 diabetes.

Official Title
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A Trial Comparing Efficacy and Safety of Insulin Degludec and Insulin Glargine in Insulin naïve Subjects With Type 2 Diabetes (BEGIN™: ONCE)

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin Degludec
* Drug: Insulin Glargine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus (diagnosed clinically) for at least 6 months Insulin naïve subjects (Allowed are: previous short term insulin treatment up to 14 days; treatment during hospitalisation or during gestational diabetes is allowed for periods longer than 14 days) Current treatment: metformin monotherapy or metformin in any combination with an insulin secretagogue (sulfonylurea or glinide), dipeptidyl peptidase IV (DPP-IV) inhibitor, alfa-glucosidase-inhibitors (acarbose) with unchanged dosing for at least 3 months prior to randomisation (Visit 2) with the minimum doses stated: metformin: alone or in combination (including fixed combination) 1500 mg daily, or maximum tolerated dose (at least 1000 mg daily), insulin secretagogue (sulfonylurea or glinide): minimum half of the daily maximal dose according to local labelling, DPP-IV inhibitor: minimum 100 mg daily or according to local labelling, alfa-glucosidase-inhibitors (acarbose): minimum half of the daily maximal dose or maximum tolerated dose HbA1c (glycosylated haemoglobin) 7.0-10.0% (both inclusive) by central laboratory analysis BMI (Body Mass Index) below or equal to 40.0 kg/m^2 Exclusion Criteria: Treatment with TZDs (thiazoledinedione), or GLP-1 (glucagon-like peptide 1) receptor agonists within the last 3 months prior to Visit 1 (screening) Anticipated change in concomitant medication known to interfere significantly with glucose metabolism, such as systemic corticosteroids, beta-blockers, MAO (monoamine oxidase) inhibitors Cardiovascular disease within the last 6 months prior to Visit 1 (screening) defined as stroke; decompensated heart failure NYHA (New York Heart Association) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty Any clinically significant disease or disorder, except for conditions associated with type 2 diabetes mellitus, which in the Investigator's opinion could interfere with the results of the trial Previous participation in this trial. Participation is defined as randomised. Re-screening of screening failures is allowed only once within the limits of the recruitment period Known or suspected hypersensitivity to trial product(s) or related products

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin Degludec<br> | Drug: Insulin Degludec<br>* Administered subcutaneously (under the skin), dose individually adjusted, once daily in combination with metformin at the unchanged, stable, pre-randomisation dose level and dosing frequency.<br>* Other names: NN1250;|
| Experimental: Insulin Glargine<br> | Drug: Insulin Glargine<br>* Administered subcutaneously (under the skin), dose individually adjusted, once daily in combination with metformin at the unchanged, stable, pre-randomisation dose level and dosing frequency.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c (%) (Analysed by Central Laboratory) | Change from baseline in HbA1c (%) after 26 weeks of treatment. | Week 0, week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Severe and Minor Treatment Emergent Hypoglycaemic Episodes | Confirmed hypoglycaemic episodes consisted of episodes of severe hypoglycaemia as well as minor hypoglycaemic episodes with a confirmed PG value of less than 3.1 mmol/L (56 mg/dL).Minor hypoglycaemic episode is defined as an episode with symptoms consistent with hypoglycaemia with confirmation by full blood glucose < 2.8 mmol/L (50 mg/dL), or PG < 3.1 mmol/L (56 mg/dL) and which is handled by the subject himself/herself or any asymptomatic full blood glucose value < 2.8 mmol/L (50 mg/dL) or PG value < 3.1 mmol/L (56 mg/dL). | On or after the first day of exposure to randomised trial drug (week 0) and no later than 7 days after last exposure to randomised trial drug (week 27) | 
| Change From Baseline in FPG (Fasting Plasma Glucose) (Analysed by Central Laboratory) | Change from baseline in FPG after 26 weeks of treatment. | Week 0, week 26 | 
| Within-subject Variability as Measured by Coefficient of Variation (CV%) in Pre-breakfast SMPG (Self-measured Plasma Glucose) | Within subject Coefficient of variation(CV[%]) in pre-breakfast self measured plasma glucose for dose adjustment after 26 treatment weeks are displayed below. | Week 26 | 
| Responder for HbA1c (Below 7.0%) at End of Trial Without Severe and Minor Hypoglycaemic Episodes | A responder for HbA1c without severe or confirmed hypoglycaemia is defined as a subject, who meets the HbA1c target at end of trial without treatment emergent severe or confirmed hypoglycaemia during the last 12 weeks of treatment or within 7 days from last treatment. | Week 26 | 
| Number of Treatment Emergent AEs (Adverse Events) | Treatment emergent events (after first trial product administration and no later than 7 days after last trial product administration) | On or after the first day of exposure to randomised trial drug (week 0) and no later than seven days after last exposure to randomised trial drug (week 27) |