The Effect of Liraglutide Versus Placebo When Added to Basal Insulin Analogues With or Without Metformin in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Asia, Europe and North and South America. The aim of the trial is to investigate the effect of liraglutide versus placebo when added to basal insulin analogues with or without metformin in subjects with type 2 diabetes.

Official Title
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The Effect of Liraglutide Versus Placebo When Added to Basal Insulin Analogues With or Without Metformin in Subjects With Type 2 Diabetes

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: liraglutide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with type 2 diabetes for at least 180 days prior to screening and treated with stable basal insulin analogue dose of minimum 20 U/day with or without stable metformin equal to or above 1500 mg/day for at least 8 weeks prior to screening (defined as insulin adjustments less than 10% during the past 8 weeks as assessed by the investigator) HbA1c (glycosylated haemoglobin A1c) 7.0-10.0% (both inclusive) Body mass index (BMI) 20-45 kg/m^2 (both inclusive) Exclusion Criteria: Female of child-bearing potential who is pregnant, breast-feeding or intending to become pregnant Recurrent severe hypoglycaemic episodes or hypoglycaemic unawareness Treatment with glucose-lowering agent(s) other than stated in the inclusion criteria in a period of 12 weeks prior to screening Impaired liver or renal function Uncontrolled treated or untreated hypertension (systolic blood pressure (SBP) equal to or above 180 mmHg and/or diastolic blood pressure (DBP) equal to or above 100 mmHg) Any clinically significant disorder, except for conditions associated with type 2 diabetes history which in the investigator's opinion could interfere with results of the trial Known or suspected abuse of alcohol or narcotics

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Liraglutide<br> | Drug: liraglutide<br>* Maximum 1.8 mg administered s.c. (subcutaneously, under the skin) once daily in addition to the subject's stable pre-trial basal insulin analogue regimen plus/minus metformin.<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* Placebo administered s.c. (subcutaneously, under the skin) once daily in addition to the subject's stable pre-trial basal insulin analogue regimen plus/minus metformin.<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 26 | The estimated mean change from baseline in HbA1c after 26 weeks of treatment. | Week 0 to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 | The estimated mean change from baseline in FPG after 26 weeks of treatment. | Week 0 to Week 26 | 
| Change in Mean Self-Measured Plasma Glucose (SMPG) of 7-Point Profile From Baseline to Week 26 | The estimated mean change from baseline in mean SMPG of 7-point profile (7-points were before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner and at bedtime) after 26 weeks of treatment. | Week 0 to Week 26 | 
| Change in Body Weight From Baseline to Week 26 | The estimated mean change in body weight after 26 weeks of treatment. | Week 0 to Week 26 | 
| Number of Subjects Achieving HbA1c Below 7.0% (American Diabetes Association [ADA] Target) | Number of subjects achieving HbA1c below 7.0% (American Diabetes Association [ADA] target) after 26 weeks of treatment | At Week 26 | 
| Number of Subjects Achieving HbA1c Below or Equal to 6.5% (American Association of Clinical Endocrinologists [AACE] Target) | Number of subjects achieving HbA1c below or equal to 6.5% (American Association of Clinical Endocrinologists [AACE] target) after 26 weeks of treatment. | At Week 26 | 
| Number of Adverse Events (AEs) During The Randomised Treatment Period | An AE was defined as treatment emergent if the onset date (or increase in severity) 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. The adverse events were categorised as 'serious' and 'non-serious' adverse events. Adverse events were also categorised according to the severity as 'mild', 'moderate' and 'severe' adverse events. | Week 0 to Week 26 + 7 days follow up | 
| Number of Minor Hypoglycaemic Episodes During The Randomised Treatment Period | A minor hypoglycaemic episode was defined as either, (a) an episode with symptoms consistent with hypoglycaemia with confirmation by blood glucose <2.8 mmol/L (50 mg/dL) or plasma glucose <3.1 mmol/L (56 mg/dL) that was handled by the subject him/herself or (b) any asymptomatic blood glucose value <2.8 mmol/L (50 mg/dL) or plasma glucose value <3.1 mmol/L (56 mg/dL). | Week 0 to Week 26 + 7 days follow up | 
| Number of Severe Hypoglycaemic Episodes During The Randomised Treatment Period | Severe hypoglycaemia episode was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions. | Week 0 to Week 26 + 7 days follow up |