Efficacy and Safety of Liraglutide in Combination With Insulin Therapy Compared to Insulin Alone in Japanese Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Asia. The purpose of the trial is to investigate the efficacy and safety of liraglutide in combination with insulin therapy compared to insulin alone in Japanese subjects with type 2 diabetes mellitus. Subjects will remain on their pre-trial insulin therapy.

Official Title
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A 36-week, Randomised, Multi-centre, Double-blind, Parallel Group Trial to Investigate the Efficacy and Safety of Liraglutide in Combination With Insulin Therapy Compared to Insulin Monotherapy in Japanese Subjects With Type 2 Diabetes Mellitus

Conditions
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Diabetes, Diabetes Mellitus, Type 2

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


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 Current insulin therapy (basal insulin, premixed insulin or basal-bolus regimen) in addition to diet and exercise therapy for at least 12 weeks prior to trial start. Their therapy is stable and fluctuation of total daily insulin dose is within plus/minus 20% for at least 12 weeks prior to trial start and current total daily insulin dose equal to or greater than 10 (I)U/day Glycosylated haemoglobin (HbA1c) between 7.5 and 11.0% (both inclusive) Body Mass Index (BMI) below 45.0 kg/m^2 Exclusion Criteria: Anticipated change in concomitant medication known to interfere significantly with glucose metabolism, such as, but not limited to systemic corticosteroids, beta-antagonists or monoamine oxidase (MAO) inhibitors Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic episode during last 12 months) or hypoglycaemic unawareness as judged by the investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months Known proliferative retinopathy or maculopathy requiring treatment according to the investigator Treatment with glucagon-like peptide-1 (GLP-1) receptor agonist within 12 weeks prior to screening Treatment with any oral antidiabetic drugs (OADs) within 12 weeks prior to screening

Ages Eligible for Study
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Minimum Age: 20 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: Lira+Insulin<br> | Drug: liraglutide<br>* Liraglutide administered subcutaneously (s.c., under the skin) for 36 weeks combined with insulin therapy.<br>Drug: insulin<br>* All subjects will continue their pre-trial insulin therapy (basal, premixed or basal-bolus regimen) during the trial. Insulin dose is fixed for the first 16 weeks and for the subsequent 20 weeks, insulin dose is individually adjusted.<br>|
| Placebo Comparator: Placebo+Insulin<br> | Drug: placebo<br>* Liraglutide placebo administered subcutaneously (s.c., under the skin) for 36 weeks combined with insulin therapy.<br>Drug: insulin<br>* All subjects will continue their pre-trial insulin therapy (basal, premixed or basal-bolus regimen) during the trial. Insulin dose is fixed for the first 16 weeks and for the subsequent 20 weeks, insulin dose is individually adjusted.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 16 | Estimated mean change from baseline in HbA1c after 16 Weeks of treatment. | Week 0, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 36 | Estimated mean change from baseline in HbA1c after 36 Weeks of treatment | Week 0, Week 36 | 
| Change in Fasting Plasma Glucose (FPG) From Baseline to Week 16 | Estimated mean change from baseline in FPG after 16 Weeks of treatment. | Week 0, Week 16 | 
| Change in Fasting Plasma Glucose (FPG) From Baseline to Week 36 | Estimated mean change from baseline in FPG after 36 Weeks of treatment. | Week 0, Week 36 | 
| Change in Mean Plasma Glucose (PG) of 7-Point Profile From Baseline to Week 16 | Estimated mean change from baseline in mean PG of 7-point profile (7-points were before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner and at bedtime) after 16 Weeks of treatment. | Week 0, Week 16 | 
| Change in Mean Plasma Glucose (PG) of 7-Point Profile From Baseline to Week 36 | Estimated mean change from baseline in mean PG of 7-point profile (7-points were before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner and at bedtime) after 36 Weeks of treatment. | Week 0, Week 36 | 
| Change in Mean Prandial PG Increment of 7-Point Profile From Baseline to Week 16 | Estimated mean change from baseline in mean prandial PG increment of 7-point profile (7-points were before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner and at bedtime) after 16 Weeks of treatment. | Week 0, Week 16 | 
| Change in Mean Prandial PG Increment of 7-Point Profile From Baseline to Week 36 | Estimated mean change from baseline in mean prandial PG increment of 7-point profile (7-points were before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner and at bedtime) after 36 Weeks of treatment. | Week 0, Week 36 | 
| Change in Body Weight From Baseline to Week 16 | Estimated mean change in body weight after 16 Weeks of treatment | Week 0, Week 16 | 
| Change in Body Weight From Baseline to Week 36 | Estimated mean change in body weight after 36 Weeks of treatment | Week 0, Week 36 | 
| Number of Adverse Events (AEs) | An AE was defined as treatment emergent if the onset date was on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. | Week 0 to Week 36 (inclusive) | 
| Number of Confirmed Hypoglycaemic Episodes | A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and until the last day on randomised treatment. Confirmed hypoglycaemic episode was defined as hypoglycaemic episodes categorised to severe and/or minor hypoglycaemic episodes. Confirmed hypoglycaemia: subject unable to treat himself/herself and/or have a recorded PG < 3.1 mmol/L (56 mg/dL). Minor: PG < 3.1 mmol/L (56 mg/dL). | Week 0 to week 36 (inclusive) |