The Effect of Insulin Degludec in Combination With Liraglutide and Metformin in Subjects With Type 2 Diabetes Qualifying for Treatment Intensification

Study Overview
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Brief Summary
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This trial is conducted in Africa, Asia, Europe and North America. The purpose of the trial is to investigate the effect of insulin degludec (IDeg) in combination with liraglutide (Lira) and metformin (at least 1500 mg daily or maximum tolerated dose) in subjects with type 2 diabetes qualifying for treatment intensification.

Official Title
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The Effect of Insulin Degludec in Combination With Liraglutide and Metformin in Subjects With Type 2 Diabetes Qualifying for Treatment Intensification

Conditions
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Diabetes, Diabetes Mellitus, Type 2

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes Insulin naïve Ongoing treatment with metformin or metformin in combination with either sulphonylurea (SU), glinides, dipeptidyl peptidase-IV (DPP-IV) inhibitors or exenatide (only twice daily (BID)) Glycosylated haemoglobin (HbA1c) (by central laboratory analysis): a. 7.5-10.0 % (both inclusive) for subjects on metformin monotherapy, b. 7.0-9.0 % (both inclusive) for subjects on metformin in combination with either SU, glinides, DPP-IV inhibitors or exenatide (only BID) Exclusion Criteria: Treatment with glucose-lowering agent(s) other than stated in the inclusion criteria within 12 weeks Calcitonin equal to or above 50 pg/mL Stroke; heart failure New York Heart Association (NYHA) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty; all within 24 weeks Current or past (within the last 5 years) malignant neoplasms (except basal cell and squamous cell carcinoma)

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IDeg + Lira<br> | Drug: insulin degludec<br>* Administered s.c. (under the skin) once daily. Dose individually adjusted.<br>Drug: liraglutide<br>* Administered s.c. (under the skin) once daily. Dose: 1.8 mg.<br>|
| Experimental: Placebo + Lira<br> | Drug: placebo<br>* Administered s.c. (under the skin) once daily. Dose individually adjusted.<br>Drug: liraglutide<br>* Administered s.c. (under the skin) once daily. Dose: 1.8 mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Haemoglobin (HbA1c) (%) | Change from baseline in HbA1c after 26 weeks of treatment | Week 0, week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose (FPG) | Change from baseline in FPG after 26 weeks of treatment | Week 0, week 26 | 
| Number of Responders for HbA1c (Below 7.0 %) | Number of responders for HbA1c below 7.0%, after 26 weeks of randomised treatment. | After 26 weeks of randomised treatment. | 
| Change From Baseline in Mean Pre-breakfast Measurements Used for Titration | Change from baseline after 26 weeks of treatment in the average of the pre-breakfast self measured plasma glucose (SMPG) measured on the day of the contact and the two days immediately prior to the contact. The least squares means presented are the estimated values after 26 weeks of treatment and the statistical analysis presents the treatment difference of the change from baseline values as the model is adjusted for baseline. | Week 0, week 26 | 
| Change From Baseline in 8-point Profile | The change from baseline in the 8-point SMPG profile after 26 weeks of randomised treatment. The least squares means presented are the estimated values after 26 weeks of treatment and the statistical analysis presents the treatment difference of the change from baseline values as the model is adjusted for baseline. | Week 0, week 26 | 
| Change From Baseline in Mean of the 8-point Profile | Change from baseline in mean of the 8-point profile after 26 weeks of randomised treatment. | Week 0, week 26 | 
| Number of Hypoglycaemic Episodes | Number of confirmed hypoglycaemic episodes from week 0 to 26 weeks of randomised treatment. A hypoglycaemic episode was defined as treatment emergent if the onset of the episode occurred after the first administration of investigational medicinal product and no later than 7 days after the last day on trial product. Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia or minor hypoglycaemic episodes. | Weeks 0 - 26 | 
| Number of Adverse Events | Number of treatment emergent AEs (TEAEs) from week 0 to week 26 of the randomised treatment. A TEAE was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. | Weeks 0 - 26 | 
| Change From Baseline in Patient Reported Health-related Quality of Life Using the Short-Form 36 Health Survey Version 2 (SF-36®v2) | Change in subject's quality of life was evaluated using the Short-Form 36 Health Survey version 2 (SF-36®v2). Evaluations were performed at baseline and at the last treatment visit (week 26). SF-36 was assessed on a scale range of 0.65 to 80.73 for physical health and -8.81 to 81.65 for mental health respectively, where higher scores indicated a better quality of life. 0-100 scores from the SF-36 were converted to a norm-based score using a T-score transformation in order to obtain a direct interpretation in relation to the distribution of the scores in the 1998 U.S. general population. | Week 0, week 26 |