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

Phase 3

Completed

Conditions: Diabetes
Diabetes Mellitus, Type 2

Interventions: Drug: exenatide
Drug: liraglutide

Registration Number: NCT00518882

Lead Sponsor: Novo Nordisk A/S

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 467

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Exenatide	exenatide	Exenatide 10 mcg twice daily + subject's own OAD treatment
Liraglutide	liraglutide	Liraglutide 1.8 mg once daily + subject's own OAD treatment

Primary Outcome Measures

Name	Time	Method
Change in Glycosylated A1c (HbA1c) at Week 26	week 0, week 26	Percentage point change in glycosylated A1c (HbA1c) from baseline (week 0) to 26 weeks (end of randomisation)

Secondary Outcome Measures

Name	Time	Method
Change in Glycosylated A1c (HbA1c), Weeks 26-78	week 26, week 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)
Change in Fasting Plasma Glucose, Weeks 26-78	week 26, week 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)
Change in Mean Prandial Increment of Plasma Glucose After Lunch, Weeks 26-78	week 26, week 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.
Change in Mean Prandial Increment of Plasma Glucose After Dinner, Weeks 26-78	week 26, week 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.
Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 78	week 0, 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.
Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 26	week 0. 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.
Change in Low-density Lipoprotein-cholesterol at Week 78	week 0, 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).
Change in Glycosylated A1c (HbA1c) at Week 78	week 0, 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)
Change in Body Weight at Week 26	week 0, week 26	Change in body weight from baseline (week 0) to 26 weeks (end of randomisation)
Change in Body Weight, Weeks 26-78	week 26, week 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)
Change in Fasting Plasma Glucose at Week 26	week 0, week 26	Change in fasting plasma glucose (FPG) from baseline (week 0) to 26 weeks (end of randomisation)
Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 26	week 0, 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.
Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 26	week 0, 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)
Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 78	week 0, 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)
Change in Body Weight at Week 78	week 0, 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)
Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 26	week 0, 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.
Change in Fasting Plasma Glucose at Week 78	week 0, 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)
Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 26	week 0, 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.
Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 26	week 0, 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.
Change in Mean Prandial Increment of Plasma Glucose After Breakfast, Weeks 26-78	week 26, week 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.
Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 78	week 0, 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.
Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 78	week 0, 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.
Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 78	week 0, 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.
Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 78	week 0, 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.
Change in Beta-cell Function at Week 26	week 0, 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).
Change in Total Cholesterol at Week 26	week 0, week 26	Change in total cholesterol (TC) from baseline (week 0) to 26 weeks (end of randomisation)
Change in Total Cholesterol, Weeks 26-78	week 26, week 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).
Change in Low-density Lipoprotein-cholesterol, Weeks 26-78	week 26, week 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).
Change in Very Low-density Lipoprotein-cholesterol at Week 26	week 0, week 26	Change in very low-density lipoprotein-cholesterol (VLDL-C) from baseline (week 0) to 26 weeks (end of randomisation)
Change in Free Fatty Acid at Week 26	week 0, week 26	Change in Free Fatty Acid (FFA) from baseline (week 0) to 26 weeks (end of randomisation)
Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 26	week 0, 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.
Change in Mean Postprandial Increment of Plasma Glucose After Dinner, Weeks 26-78	week 26, week 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.
Change in Total Cholesterol at Week 78	week 0, 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).
Change in Mean Postprandial Increment of Plasma Glucose After Breakfast, Weeks 26-78	week 26, week 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.
Change in Mean Postprandial Increment of Plasma Glucose After Lunch, Weeks 26-78	week 26, week 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.
Change in Beta-cell Function, Weeks 26-78	week 26, week 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).
Change in Beta-cell Function at Week 78	week 0, 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).
Change in Low-density Lipoprotein-cholesterol at Week 26	week 0, week 26	Change in Low-density Lipoprotein-cholesterol (LDL-C) from baseline (week 0) to 26 weeks (end of randomisation)
Change in High-density Lipoprotein-cholesterol, Weeks 26-78	week 26, week 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).
Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 78	week 0, 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.
Change in High-density Lipoprotein-cholesterol at Week 78	week 0, 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).
Change in Very Low-density Lipoprotein-cholesterol, Weeks 26-78	week 26, week 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).
Change in Triglyceride at Week 26	week 0, week 26	Change in triglyceride (TG) from from baseline (week 0) to 26 weeks (end of randomisation)
Change in Apolipoprotein B at Week 26	week 0, week 26	Change in apolipoprotein B (ApoB) from baseline (week 0) to 26 weeks (end of randomisation)
Hypoglycaemic Episodes at Week 26	weeks 0-26	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.
Change in Very Low-density Lipoprotein-cholesterol at Week 78	week 0, 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).
Change in High-density Lipoprotein-cholesterol at Week 26	week 0, week 26	Change in High-density Lipoprotein-cholesterol (HDL-C) from baseline (week 0) to 26 weeks (end of randomisation)
Change in Triglyceride at Week 78	week 0, 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).
Change in Triglyceride, Weeks 26-78	week 26, week 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).
Change in Apolipoprotein B, Weeks 26-78	week 26, week 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).
Change in Free Fatty Acid, Weeks 26-78	week 26, week 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).
Change in Free Fatty Acid at Week 78	week 0, 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).
Change in Apolipoprotein B at Week 78	week 0, 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).
Hypoglyceamic Episodes, Weeks 26-78	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.