Comparison of the Efficacy and Safety of Two Intensification Strategies in Subjects With Type 2 Diabetes Inadequately Controlled on Basal Insulin and Metformin

Study Overview
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Brief Summary
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This trial is conducted in Europe and North America. The aim of this trial is to compare the efficacy and safety of adding liraglutide versus addition of insulin aspart with the largest meal to insulin degludec in subjects with type 2 diabetes. Eligible subjects with an HbA1c equal to or above 7% at end of treatment in NN1250-3643 (NCT01193309) trial will be randomised to receive treatment intensification while subjects with an HbA1c below 7% at end of treatment in NN1250-3643 (NCT01193309) may continue to receive insulin degludec treatment. Subjects are to continue their pre-trial metformin treatment.

Official Title
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A Trial Comparing the Efficacy and Safety of Adding Liraglutide Versus Addition of Insulin Aspart With the Largest Meal to Insulin Degludec, Both in Combination With Metformin, in Subjects With Type 2 Diabetes Qualifying for Treatment Intensification (BEGIN™: VICTOZA® ADD-ON)

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: insulin degludec
* Drug: insulin aspart
* Drug: liraglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject). The subject must have completed the end of treatment visit of NN1250-3643 with Insulin degludec once daily + metformin. Ability and willingness to adhere to the protocol including self measurement of plasma glucose according to the protocol Exclusion Criteria: Participated in NN1250-3643 and treated with insulin glargine Previous treatment with glucacon like peptide (GLP-1) receptor agonists (e.g. exenatide, liraglutide) Impaired liver function, defined as alanine aminotransferase (ALAT) 2.5 times the upper limit of normal at end of treatment in NN1250-3643 Impaired renal function defined as serum-creatinine = 125 µmol/l (= 1.4 mg/dl) for males and = 110 µmol/L (= 1.3 mg/dl) for females or according to local label for metformin [For France: glomerular filtration rate below 60 ml/min, calculated by the Cockroft & Gault formula] at end of treatment in NN1250-3643.

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: IDeg (non-randomised)<br> | Drug: insulin degludec<br>* Injected s.c. (under the skin) once daily. The doses will be individually adjusted<br>|
| Experimental: IDeg + IAsp<br> | Drug: insulin degludec<br>* Injected s.c. (under the skin) once daily. The doses will be individually adjusted<br>Drug: insulin aspart<br>* Injected s.c. (under the skin) once daily. The doses will be individually adjusted.<br>|
| Experimental: IDeg + liraglutide<br> | Drug: insulin degludec<br>* Injected s.c. (under the skin) once daily. The doses will be individually adjusted<br>Drug: liraglutide<br>* Injected s.c. (under the skin) once daily. The doses will be individually adjusted.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c (%) (Glycosylated Haemoglobin) | Values for change in HbA1c from baseline to 26 weeks of treatment period. | week 0, week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose (FPG) | Values for change in FPG in mmol/L from baseline to week 26 of randomised period. | week 0, week 26 | 
| Change From Baseline in Body Weight | Corresponds to the values of change in body weight in kilograms from baseline to week 26. | week 0, week 26 | 
| Number of Severe and Minor Treatment Emergent Hypoglycaemic Episodes | Corresponds to number of treatment emergent hypoglycaemic events from onset on or after the first day of exposure to investigational product and no later than 7 days after last exposure to investigational product. Confirmed hypoglycaemia was defined as the pool of severe hypoglycaemic episodes and minor episodes with a plasma glucose (PG) value < 3.1 mmol/L (56 mg/dL). | Onset on or after the first day of exposure to investigational product for 26 weeks of treatment period and no later than 7 days after last exposure to investigational product. |