Effect of Liraglutide or Exenatide Added to an Ongoing Treatment on Blood Glucose Control in Subjects With Type 2 Diabetes (LEAD-6)

This study has been completed.
Sponsor:
Information provided by:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00518882
First received: August 20, 2007
Last updated: June 19, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Diabetes
Diabetes Mellitus, Type 2
Drug: liraglutide
Drug: exenatide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novo Nordisk A/S:

Primary Outcome Measures:
  • Change in Glycosylated A1c (HbA1c) at Week 26 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]
    Percentage point change in glycosylated A1c (HbA1c) from baseline (week 0) to 26 weeks (end of randomisation)


Secondary Outcome Measures:
  • Change in Glycosylated A1c (HbA1c), Weeks 26-78 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]
    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 Glycosylated A1c (HbA1c) at Week 78 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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)

  • Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 26 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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 26 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]
    Change in body weight from baseline (week 0) to 26 weeks (end of randomisation)

  • Change in Body Weight, Weeks 26-78 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]
    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 Body Weight at Week 78 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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 Fasting Plasma Glucose at Week 26 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]
    Change in fasting plasma glucose (FPG) from baseline (week 0) to 26 weeks (end of randomisation)

  • Change in Fasting Plasma Glucose, Weeks 26-78 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]
    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 Fasting Plasma Glucose at Week 78 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]
    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 Lunch at Week 26 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]
    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.

  • Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 26 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]
    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 Lunch, Weeks 26-78 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]
    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 Breakfast at Week 78 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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 Prandial Increment of Plasma Glucose After Dinner at Week 78 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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 Breakfast at Week 26 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]
    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 Lunch at Week 26 [ Time Frame: week 0. week 26 ] [ Designated as safety issue: No ]
    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 Mean Postprandial Increment of Plasma Glucose After Dinner at Week 26 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]
    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 Mean Postprandial Increment of Plasma Glucose After Breakfast, Weeks 26-78 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]
    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 Mean Postprandial Increment of Plasma Glucose After Dinner, Weeks 26-78 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]
    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 Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 78 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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 Mean Postprandial Increment of Plasma Glucose After Dinner at Week 78 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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 Beta-cell Function at Week 26 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]

    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 Beta-cell Function, Weeks 26-78 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]

    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 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]

    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 Total Cholesterol at Week 26 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]
    Change in total cholesterol (TC) from baseline (week 0) to 26 weeks (end of randomisation)

  • Change in Total Cholesterol, Weeks 26-78 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]
    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 Total Cholesterol at Week 78 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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 Low-density Lipoprotein-cholesterol at Week 26 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]
    Change in Low-density Lipoprotein-cholesterol (LDL-C) from baseline (week 0) to 26 weeks (end of randomisation)

  • Change in Low-density Lipoprotein-cholesterol, Weeks 26-78 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]
    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 Low-density Lipoprotein-cholesterol at Week 78 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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 Very Low-density Lipoprotein-cholesterol at Week 26 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]
    Change in very low-density lipoprotein-cholesterol (VLDL-C) from baseline (week 0) to 26 weeks (end of randomisation)

  • Change in Very Low-density Lipoprotein-cholesterol, Weeks 26-78 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]
    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 Very Low-density Lipoprotein-cholesterol at Week 78 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]
    Change in High-density Lipoprotein-cholesterol (HDL-C) from baseline (week 0) to 26 weeks (end of randomisation)

  • Change in High-density Lipoprotein-cholesterol, Weeks 26-78 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]
    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 High-density Lipoprotein-cholesterol at Week 78 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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 Triglyceride at Week 26 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]
    Change in triglyceride (TG) from from baseline (week 0) to 26 weeks (end of randomisation)

  • Change in Triglyceride, Weeks 26-78 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]
    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 Triglyceride at Week 78 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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 Free Fatty Acid at Week 26 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]
    Change in Free Fatty Acid (FFA) from baseline (week 0) to 26 weeks (end of randomisation)

  • Change in Free Fatty Acid, Weeks 26-78 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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 26 [ Time Frame: week 0, week 26 ] [ Designated as safety issue: No ]
    Change in apolipoprotein B (ApoB) from baseline (week 0) to 26 weeks (end of randomisation)

  • Change in Apolipoprotein B, Weeks 26-78 [ Time Frame: week 26, week 78 ] [ Designated as safety issue: No ]
    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 Apolipoprotein B at Week 78 [ Time Frame: week 0, week 78 ] [ Designated as safety issue: No ]
    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).

  • Hypoglycaemic Episodes at Week 26 [ Time Frame: weeks 0-26 ] [ Designated as safety issue: Yes ]
    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.

  • Hypoglyceamic Episodes, Weeks 26-78 [ Time Frame: weeks 26-78 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 467
Study Start Date: August 2007
Study Completion Date: April 2009
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Liraglutide
Liraglutide 1.8 mg once daily + subject's own OAD treatment
Drug: liraglutide
1.8 mg once daily for s.c. (under the skin) injection.
Active Comparator: Exenatide
Exenatide 10 mcg twice daily + subject's own OAD treatment
Drug: exenatide
10 mcg twice daily for s.c. (under the skin) injection.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00518882

  Show 63 Study Locations
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Marcin Zychma, MD, PhD Novo Nordisk A/S
  More Information

Additional Information:
No publications provided by Novo Nordisk A/S

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Public Access to Clinical Trials, Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00518882     History of Changes
Other Study ID Numbers: NN2211-1797, 2006-006092-21
Study First Received: August 20, 2007
Results First Received: February 23, 2010
Last Updated: June 19, 2012
Health Authority: United States: Food and Drug Administration
Finland: Finnish Medicines Agency
Switzerland: Swissmedic
Germany: Federal Institute for Drugs and Medical Devices
Ireland: Irish Medicines Board
Austria: Federal Ministry for Health and Women
Poland: The Office for Registration of Medicinal Products, Medical Devices; and Biocides, Central Evidence of Clinical Trials
Denmark: Danish Medicines Agency
Macedonia, The Former Yugoslav Republic of: Drug Agency, Ministry of Health
Slovenia: Agency of Drugs and Medicinal Products of the Slovenian Republic
Romania: National Medicines Agency
Sweden: Medical Products Agency

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Exenatide
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on April 23, 2014