Effect of Liraglutide or Exenatide Added to an Ongoing Treatment on Blood Glucose Control in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Europe and the United States of America (USA). The aim of this trial is to compare the effect on glycaemic control of liraglutide or exenatide when added to subject's ongoing OAD (oral anti-diabetic drug) treatment of either metformin, sulphonylurea or a combination of both in subjects with type 2 diabetes. Two trial periods: A 26 week randomised, followed by a 52 week extension (14 + 38 weeks) where all subjects received liraglutide + OAD after previous randomisation to either liraglutide or exenatide, both combined with OAD treatment.

Official Title
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Effect of Liraglutide or Exenatide Added to a Background Treatment of Metformin, Sulphonylurea or a Combination of Both on Glycaemic Control 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: exenatide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes Stable treatment with Oral Anti-Diabetic Drugs (metformin, sulphonylurea or a combination of both) for at least 3 months at the discretion of the Investigator HbA1C equal to or greater than 7.0% and equal to or lower than 11.0% Body Mass Index (BMI) equal to or lower than 45.0 kg/m2 Exclusion Criteria: Previous treatment with insulin Treatment with any anti-diabetic drug other than metformin and sulphonylurea Any previous exposure to exenatide or liraglutide Impaired liver or/and renal function History of any significant cardiac events Known retinopathy or maculopathy requiring acute treatment Recurrent major hypoglycaemia or hypoglycaemic unawareness

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide<br>Liraglutide 1.8 mg once daily + subject's own OAD treatment | Drug: liraglutide<br>* 1.8 mg once daily for s.c. (under the skin) injection.<br>|
| Active Comparator: Exenatide<br>Exenatide 10 mcg twice daily + subject's own OAD treatment | Drug: exenatide<br>* 10 mcg twice daily for s.c. (under the skin) injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated A1c (HbA1c) at Week 26 | Percentage point change in glycosylated A1c (HbA1c) from baseline (week 0) to 26 weeks (end of randomisation) | week 0, week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated A1c (HbA1c), Weeks 26-78 | Percentage point change in glycosylated A1c (HbA1c) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group) | week 26, week 78 | 
| Change in Glycosylated A1c (HbA1c) at Week 78 | Percentage point change in glycosylated A1c (HbA1c) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group) | week 0, week 78 | 
| Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 26 | Percentage of subjects achieving treatment target of HbA1c less than 7.0% or less than or equal to 6.5% at Week 26 (end of randomisation) | week 0, week 26 | 
| Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 78 | Percentage of subjects achieving treatment target of HbA1c less than 7.0% or less than or equal to 6.5% at Week 78 (end of treatment) | week 0, week 78 | 
| Change in Body Weight at Week 26 | Change in body weight from baseline (week 0) to 26 weeks (end of randomisation) | week 0, week 26 | 
| Change in Body Weight, Weeks 26-78 | Change in body weight from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group) | week 26, week 78 | 
| Change in Body Weight at Week 78 | Change in body weight from baseline (Week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group) | week 0, week 78 | 
| Change in Fasting Plasma Glucose at Week 26 | Change in fasting plasma glucose (FPG) from baseline (week 0) to 26 weeks (end of randomisation) | week 0, week 26 | 
| Change in Fasting Plasma Glucose, Weeks 26-78 | Change in fasting plasma glucose from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group) | week 26, week 78 | 
| Change in Fasting Plasma Glucose at Week 78 | Change in fasting plasma glucose from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group) | week 0, week 78 | 
| Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 26 | Change in mean prandial increment of plasma glucose after breakfast from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between glucose values measured before and after breakfast. | week 0, week 26 | 
| Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 26 | Change in mean prandial increment of plasma glucose after lunch from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch. | week 0, week 26 | 
| Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 26 | Change in mean prandial increment of plasma glucose after dinner from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner. | week 0, week 26 | 
| Change in Mean Prandial Increment of Plasma Glucose After Breakfast, Weeks 26-78 | Change in mean prandial increment of plasma glucose after breakfast from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast. | week 26, week 78 | 
| Change in Mean Prandial Increment of Plasma Glucose After Lunch, Weeks 26-78 | Change in mean prandial increment of plasma glucose after lunch from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after a lunch. | week 26, week 78 | 
| Change in Mean Prandial Increment of Plasma Glucose After Dinner, Weeks 26-78 | Change in mean prandial increment of plasma glucose after dinner from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner. | week 26, week 78 | 
| Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 78 | Change in mean prandial increment of plasma glucose after breakfast from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast. | week 0, week 78 | 
| Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 78 | Change in mean prandial increment of plasma glucose after lunch from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch. | week 0, week 78 | 
| Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 78 | Change in mean prandial increment of plasma glucose after dinner from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner. | week 0, week 78 | 
| Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 26 | Change in mean postprandial increment of plasma glucose after breakfast from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast. | week 0, week 26 | 
| Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 26 | Change in mean postprandial increment of plasma glucose after lunch from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch. | week 0. week 26 | 
| Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 26 | Change in mean postprandial increment of plasma glucose after dinner from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner. | week 0, week 26 | 
| Change in Mean Postprandial Increment of Plasma Glucose After Breakfast, Weeks 26-78 | Change in mean postprandial increment of plasma glucose after breakfast from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast. | week 26, week 78 | 
| Change in Mean Postprandial Increment of Plasma Glucose After Lunch, Weeks 26-78 | Change in mean postprandial increment of plasma glucose after lunch from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch. | week 26, week 78 | 
| Change in Mean Postprandial Increment of Plasma Glucose After Dinner, Weeks 26-78 | Change in mean postprandial increment of plasma glucose after dinner from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner. | week 26, week 78 | 
| Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 78 | Change in mean postprandial increment of plasma glucose after breakfast from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast. | week 0, week 78 | 
| Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 78 | Change in mean postprandial increment of plasma glucose after lunch from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch. | week 0, week 78 | 
| Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 78 | Change in mean postprandial increment of plasma glucose after dinner from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner. | week 0, week 78 | 
| Change in Beta-cell Function at Week 26 | Change in Beta-cell function from baseline (week 0) to 26 weeks (end of randomisation). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B). Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5). | week 0, week 26 | 
| Change in Beta-cell Function, Weeks 26-78 | Change in Beta-cell function from Week 26 (end of randomisation) to Week 78 (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B). Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5). | week 26, week 78 | 
| Change in Beta-cell Function at Week 78 | Change in Beta-cell function from baseline (week 0) to 78 weeks (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B). Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5). | week 0, week 78 | 
| Change in Total Cholesterol at Week 26 | Change in total cholesterol (TC) from baseline (week 0) to 26 weeks (end of randomisation) | week 0, week 26 | 
| Change in Total Cholesterol, Weeks 26-78 | Change in total cholesterol (TC) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group). | week 26, week 78 | 
| Change in Total Cholesterol at Week 78 | Change in total cholesterol (TC) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group). | week 0, week 78 | 
| Change in Low-density Lipoprotein-cholesterol at Week 26 | Change in Low-density Lipoprotein-cholesterol (LDL-C) from baseline (week 0) to 26 weeks (end of randomisation) | week 0, week 26 | 
| Change in Low-density Lipoprotein-cholesterol, Weeks 26-78 | Change in low-density lipoprotein-cholesterol (LDL-C) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group). | week 26, week 78 | 
| Change in Low-density Lipoprotein-cholesterol at Week 78 | Change in Low-density Lipoprotein-cholesterol (LDL-C) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group). | week 0, week 78 | 
| Change in Very Low-density Lipoprotein-cholesterol at Week 26 | Change in very low-density lipoprotein-cholesterol (VLDL-C) from baseline (week 0) to 26 weeks (end of randomisation) | week 0, week 26 | 
| Change in Very Low-density Lipoprotein-cholesterol, Weeks 26-78 | Change in Very Low-density Lipoprotein-cholesterol (VLDL-C) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group). | week 26, week 78 | 
| Change in Very Low-density Lipoprotein-cholesterol at Week 78 | Change in Very Low-density Lipoprotein-cholesterol (VLDL-C) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group). | week 0, week 78 | 
| Change in High-density Lipoprotein-cholesterol at Week 26 | Change in High-density Lipoprotein-cholesterol (HDL-C) from baseline (week 0) to 26 weeks (end of randomisation) | week 0, week 26 | 
| Change in High-density Lipoprotein-cholesterol, Weeks 26-78 | Change in High-density Lipoprotein-cholesterol (HDL-C) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group). | week 26, week 78 | 
| Change in High-density Lipoprotein-cholesterol at Week 78 | Change in High-density Lipoprotein-cholesterol (HDL-C) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group). | week 0, week 78 | 
| Change in Triglyceride at Week 26 | Change in triglyceride (TG) from from baseline (week 0) to 26 weeks (end of randomisation) | week 0, week 26 | 
| Change in Triglyceride, Weeks 26-78 | Change in Triglyceride (TG) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group). | week 26, week 78 | 
| Change in Triglyceride at Week 78 | Change in triglyceride (TG) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group). | week 0, week 78 | 
| Change in Free Fatty Acid at Week 26 | Change in Free Fatty Acid (FFA) from baseline (week 0) to 26 weeks (end of randomisation) | week 0, week 26 | 
| Change in Free Fatty Acid, Weeks 26-78 | Change in Free Fatty Acid (FFA) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group). | week 26, week 78 | 
| Change in Free Fatty Acid at Week 78 | Change in Free Fatty Acid (FFA) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group). | week 0, week 78 | 
| Change in Apolipoprotein B at Week 26 | Change in apolipoprotein B (ApoB) from baseline (week 0) to 26 weeks (end of randomisation) | week 0, week 26 | 
| Change in Apolipoprotein B, Weeks 26-78 | Change in apolipoprotein B (ApoB) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group). | week 26, week 78 | 
| Change in Apolipoprotein B at Week 78 | Change in apolipoprotein B (ApoB) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group). | week 0, week 78 | 
| Hypoglycaemic Episodes at Week 26 | Total number of hypoglycaemic episodes occurring after baseline (week 0) and until week 26 (end of randomisation). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. | weeks 0-26 | 
| Hypoglyceamic Episodes, Weeks 26-78 | Total number of hypoglycaemic episodes occurring after end of randomisation (week 26) and until week 78 (end of treatment). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. | weeks 26-78 |