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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: liraglutide; Drug: exenatide

• Study Type: Interventional
• Enrollment (Actual): 467
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1130
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1030
    • Novo Nordisk Investigational Site
• Denmark
  • Aalborg, Denmark, 9000
    • Novo Nordisk Investigational Site
  • Gentofte, Denmark, 2820
    • Novo Nordisk Investigational Site
  • Hvidovre, Denmark, 2650
    • Novo Nordisk Investigational Site
  • Odense, Denmark, 5000
    • Novo Nordisk Investigational Site
  • Århus C, Denmark, 8000
    • Novo Nordisk Investigational Site
• Finland
  • Helsinki, Finland, 00029
    • Novo Nordisk Investigational Site
  • Lahti, Finland, 15110
    • Novo Nordisk Investigational Site
  • Oulu, Finland, FI-90100
    • Novo Nordisk Investigational Site
• France
  • Antibes, France, 06600
    • Novo Nordisk Investigational Site
  • Dommartin Les Toul, France, 54201
    • Novo Nordisk Investigational Site
  • LA ROCHELLE cedex, France, 17019
    • Novo Nordisk Investigational Site
  • NEVERS cedex, France, 58033
    • Novo Nordisk Investigational Site
  • Narbonne, France, 11108
    • Novo Nordisk Investigational Site
• Germany
  • Bochum, Germany, 44791
    • Novo Nordisk Investigational Site
  • Dreieich-Sprendlingen, Germany, 63303
    • Novo Nordisk Investigational Site
  • Falkensee, Germany, 14612
    • Novo Nordisk Investigational Site
  • Frankfurt, Germany, 60388
    • Novo Nordisk Investigational Site
  • Hamburg, Germany, 22607
    • Novo Nordisk Investigational Site
  • Hannover, Germany, 30625
    • Novo Nordisk Investigational Site
  • Herrenberg, Germany, 71083
    • Novo Nordisk Investigational Site
  • Lampertheim, Germany, 68623
    • Novo Nordisk Investigational Site
  • Ludwigshafen, Germany, 67059
    • Novo Nordisk Investigational Site
  • Marburg, Germany, 35039
    • Novo Nordisk Investigational Site
  • Pohlheim, Germany, 35415
    • Novo Nordisk Investigational Site
  • Rehlingen-Siersburg, Germany, 66780
    • Novo Nordisk Investigational Site
  • Speyer, Germany, 67346
    • Novo Nordisk Investigational Site
  • Tübingen, Germany, 72072
    • Novo Nordisk Investigational Site
• Ireland
  • Dublin, Ireland, DUBLIN 7
    • Novo Nordisk Investigational Site
  • Dublin, Ireland, DUBLIN 8
    • Novo Nordisk Investigational Site
  • Dublin 24, Ireland
    • Novo Nordisk Investigational Site
  • Dublin 9, Ireland
    • Novo Nordisk Investigational Site
• Macedonia, The Former Yugoslav Republic of
  • Skopje, Macedonia, The Former Yugoslav Republic of, 1000
    • Novo Nordisk Investigational Site
• Norway
  • Bergen, Norway, 5021
    • Novo Nordisk Investigational Site
  • Bergen, Norway, NO-5012
    • Novo Nordisk Investigational Site
  • Stavanger, Norway, 4011
    • Novo Nordisk Investigational Site
  • Trondheim, Norway, NO-7030
    • Novo Nordisk Investigational Site
• Poland
  • Bydgoszcz, Poland, 85-822
    • Novo Nordisk Investigational Site
  • Gniewkowo, Poland, 88-140
    • Novo Nordisk Investigational Site
  • Krakow, Poland, 31-501
    • Novo Nordisk Investigational Site
  • Lublin, Poland, 20-081
    • Novo Nordisk Investigational Site
  • Poznan, Poland, 60-821
    • Novo Nordisk Investigational Site
  • Tychy, Poland, 43-100
    • Novo Nordisk Investigational Site
  • Warszawa, Poland, 01-911
    • Novo Nordisk Investigational Site
  • Wroclaw, Poland, 50-127
    • Novo Nordisk Investigational Site
  • Zabrze, Poland, 41-800
    • Novo Nordisk Investigational Site
• Puerto Rico
  • Manati, Puerto Rico, 00674
    • Novo Nordisk Investigational Site
• Romania
  • Resita, Romania, 320076
    • Novo Nordisk Investigational Site
  • Suceava, Romania, 720237
    • Novo Nordisk Investigational Site
  • Alba
    • Alba Iulia, Alba, Romania, 510053
      • Novo Nordisk Investigational Site
• Slovenia
  • Koper, Slovenia, SI-6000
    • Novo Nordisk Investigational Site
  • Ljubljana, Slovenia, 1525
    • Novo Nordisk Investigational Site
  • Novo mesto, Slovenia, 8000
    • Novo Nordisk Investigational Site
• Spain
  • Hospitalet de Llobregat, Spain, 08907
    • Novo Nordisk Investigational Site
  • Oviedo, Spain, 33006
    • Novo Nordisk Investigational Site
  • Palma de Mallorca, Spain, 07010
    • Novo Nordisk Investigational Site
  • Puerto del Rosario, Spain, 35600
    • Novo Nordisk Investigational Site
• Sweden
  • Stockholm, Sweden, 171 76
    • Novo Nordisk Investigational Site
  • Stockholm, Sweden, 141 86
    • Novo Nordisk Investigational Site
• Switzerland
  • Basel, Switzerland, 4031
    • Novo Nordisk Investigational Site
  • Bern, Switzerland, 3010
    • Novo Nordisk Investigational Site
  • Genève 14, Switzerland, 1211
    • Novo Nordisk Investigational Site
  • Lugano, Switzerland, 6900
    • Novo Nordisk Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35242
      • Novo Nordisk Investigational Site
  • Arizona
    • Goodyear, Arizona, United States, 85395
      • Novo Nordisk Investigational Site
  • California
    • Artesia, California, United States, 90701
      • Novo Nordisk Investigational Site
    • Encino, California, United States, 91436
      • Novo Nordisk Investigational Site
    • Escondido, California, United States, 92025
      • Novo Nordisk Investigational Site
    • Los Angeles, California, United States, 90057
      • Novo Nordisk Investigational Site
    • Orange, California, United States, 92869
      • Novo Nordisk Investigational Site
    • Sacramento, California, United States, 95816
      • Novo Nordisk Investigational Site
    • San Mateo, California, United States, 94401
      • Novo Nordisk Investigational Site
    • Spring Valley, California, United States, 91978
      • Novo Nordisk Investigational Site
    • Walnut Creek, California, United States, 94598
      • Novo Nordisk Investigational Site
  • Florida
    • Fort Myers, Florida, United States, 33907
      • Novo Nordisk Investigational Site
    • Hollywood, Florida, United States, 33023
      • Novo Nordisk Investigational Site
    • Jacksonville, Florida, United States, 32216
      • Novo Nordisk Investigational Site
    • Jacksonville, Florida, United States, 32205
      • Novo Nordisk Investigational Site
    • Jacksonville, Florida, United States, 32259
      • Novo Nordisk Investigational Site
    • Longwood, Florida, United States, 32779
      • Novo Nordisk Investigational Site
    • Ocala, Florida, United States, 34471
      • Novo Nordisk Investigational Site
    • Pembroke Pines, Florida, United States, 33029
      • Novo Nordisk Investigational Site
    • Plantation, Florida, United States, 33324
      • Novo Nordisk Investigational Site
    • St. Cloud, Florida, United States, 34769
      • Novo Nordisk Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Novo Nordisk Investigational Site
    • Powder Springs, Georgia, United States, 30127
      • Novo Nordisk Investigational Site
    • Roswell, Georgia, United States, 30076
      • Novo Nordisk Investigational Site
  • Idaho
    • Idaho Falls, Idaho, United States, 83404-7596
      • Novo Nordisk Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60616
      • Novo Nordisk Investigational Site
    • Peoria, Illinois, United States, 61615
      • Novo Nordisk Investigational Site
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Novo Nordisk Investigational Site
  • Iowa
    • Des Moines, Iowa, United States, 50314-3027
      • Novo Nordisk Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Novo Nordisk Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55416
      • Novo Nordisk Investigational Site
    • St. Paul, Minnesota, United States, 55108
      • Novo Nordisk Investigational Site
  • Missouri
    • St. Peters, Missouri, United States, 63376
      • Novo Nordisk Investigational Site
  • New Jersey
    • Flemington, New Jersey, United States, 08822
      • Novo Nordisk Investigational Site
    • South Bound Brook, New Jersey, United States, 08880
      • Novo Nordisk Investigational Site
  • New York
    • Northport, New York, United States, 11768
      • Novo Nordisk Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • Novo Nordisk Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • Novo Nordisk Investigational Site
    • Cincinnati, Ohio, United States, 45206
      • Novo Nordisk Investigational Site
    • Dayton, Ohio, United States, 45439
      • Novo Nordisk Investigational Site
    • Kettering, Ohio, United States, 45429
      • Novo Nordisk Investigational Site
    • Mentor, Ohio, United States, 44060
      • Novo Nordisk Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Novo Nordisk Investigational Site
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Novo Nordisk Investigational Site
    • Philadelphia, Pennsylvania, United States, 19152
      • Novo Nordisk Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15213
      • Novo Nordisk Investigational Site
  • South Carolina
    • Sumter, South Carolina, United States, 29150
      • Novo Nordisk Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Novo Nordisk Investigational Site
  • Texas
    • Austin, Texas, United States, 78731
      • Novo Nordisk Investigational Site
    • Corpus Christi, Texas, United States, 78412
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75230
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75231
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75246
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77030
      • Novo Nordisk Investigational Site
    • Midland, Texas, United States, 79707
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78229
      • Novo Nordisk Investigational Site
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Novo Nordisk Investigational Site
    • Richmond, Virginia, United States, 23294
      • Novo Nordisk Investigational Site
  • Washington
    • Olympia, Washington, United States, 98502
      • Novo Nordisk Investigational Site
    • Spokane, Washington, United States, 99218
      • Novo Nordisk Investigational Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53209
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Henry RR, Buse JB, Sesti G, Davies MJ, Jensen KH, Brett J, Pratley RE. Efficacy of antihyperglycemic therapies and the influence of baseline hemoglobin A(1C): a meta-analysis of the liraglutide development program. Endocr Pract. 2011 Nov-Dec;17(6):906-13. doi: 10.4158/ep.17.6.906.
• Zinman B, Schmidt WE, Moses A, Lund N, Gough S. Achieving a clinically relevant composite outcome of an HbA1c of <7% without weight gain or hypoglycaemia in type 2 diabetes: a meta-analysis of the liraglutide clinical trial programme. Diabetes Obes Metab. 2012 Jan;14(1):77-82. doi: 10.1111/j.1463-1326.2011.01493.x. Epub 2011 Oct 30.
• Niswender K, Pi-Sunyer X, Buse J, Jensen KH, Toft AD, Russell-Jones D, Zinman B. Weight change with liraglutide and comparator therapies: an analysis of seven phase 3 trials from the liraglutide diabetes development programme. Diabetes Obes Metab. 2013 Jan;15(1):42-54. doi: 10.1111/j.1463-1326.2012.01673.x. Epub 2012 Sep 9.
• Alves C, Batel-Marques F, Macedo AF. A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer. Diabetes Res Clin Pract. 2012 Nov;98(2):271-84. doi: 10.1016/j.diabres.2012.09.008. Epub 2012 Sep 23.
• King AB, Montanya E, Pratley RE, Blonde L, Svendsen CB, Donsmark M, Sesti G. Liraglutide achieves A1C targets more often than sitagliptin or exenatide when added to metformin in patients with type 2 diabetes and a baseline A1C <8.0%. Endocr Pract. 2013 Jan-Feb;19(1):64-72. doi: 10.4158/EP12232.OR.
• Jensen TM, Saha K, Steinberg WM. Is there a link between liraglutide and pancreatitis? A post hoc review of pooled and patient-level data from completed liraglutide type 2 diabetes clinical trials. Diabetes Care. 2015 Jun;38(6):1058-66. doi: 10.2337/dc13-1210. Epub 2014 Dec 12. Erratum In: Diabetes Care. 2015 Aug;38(8):1622.
• Davidson JA, Orsted DD, Campos C. Efficacy and safety of liraglutide, a once-daily human glucagon-like peptide-1 analogue, in Latino/Hispanic patients with type 2 diabetes: post hoc analysis of data from four phase III trials. Diabetes Obes Metab. 2016 Jul;18(7):725-8. doi: 10.1111/dom.12653. Epub 2016 Apr 28.
• Sullivan SD, Alfonso-Cristancho R, Conner C, Hammer M, Blonde L. Long-term outcomes in patients with type 2 diabetes receiving glimepiride combined with liraglutide or rosiglitazone. Cardiovasc Diabetol. 2009 Feb 26;8:12. doi: 10.1186/1475-2840-8-12.
• McGill JB. Insights from the Liraglutide Clinical Development Program--the Liraglutide Effect and Action in Diabetes (LEAD) studies. Postgrad Med. 2009 May;121(3):16-25. doi: 10.3810/pgm.2009.05.1998.
• Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L; LEAD-6 Study Group. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet. 2009 Jul 4;374(9683):39-47. doi: 10.1016/S0140-6736(09)60659-0. Epub 2009 Jun 8.
• Buse JB, Sesti G, Schmidt WE, Montanya E, Chang CT, Xu Y, Blonde L, Rosenstock J; Liraglutide Effect Action in Diabetes-6 Study Group. Switching to once-daily liraglutide from twice-daily exenatide further improves glycemic control in patients with type 2 diabetes using oral agents. Diabetes Care. 2010 Jun;33(6):1300-3. doi: 10.2337/dc09-2260. Epub 2010 Mar 23.
• Schmidt WE, Christiansen JS, Hammer M, Zychma MJ, Buse JB. Patient-reported outcomes are superior in patients with Type 2 diabetes treated with liraglutide as compared with exenatide, when added to metformin, sulphonylurea or both: results from a randomized, open-label study. Diabet Med. 2011 Jun;28(6):715-23. doi: 10.1111/j.1464-5491.2011.03276.x.
• Buse JB, Garber A, Rosenstock J, Schmidt WE, Brett JH, Videbaek N, Holst J, Nauck M. Liraglutide treatment is associated with a low frequency and magnitude of antibody formation with no apparent impact on glycemic response or increased frequency of adverse events: results from the Liraglutide Effect and Action in Diabetes (LEAD) trials. J Clin Endocrinol Metab. 2011 Jun;96(6):1695-702. doi: 10.1210/jc.2010-2822. Epub 2011 Mar 30.
• Valentine WJ, Palmer AJ, Lammert M, Langer J, Brandle M. Evaluating the long-term cost-effectiveness of liraglutide versus exenatide BID in patients with type 2 diabetes who fail to improve with oral antidiabetic agents. Clin Ther. 2011 Nov;33(11):1698-712. doi: 10.1016/j.clinthera.2011.09.022. Epub 2011 Oct 21.
• Bode BW, Brett J, Falahati A, Pratley RE. Comparison of the efficacy and tolerability profile of liraglutide, a once-daily human GLP-1 analog, in patients with type 2 diabetes >/=65 and <65 years of age: a pooled analysis from phase III studies. Am J Geriatr Pharmacother. 2011 Dec;9(6):423-33. doi: 10.1016/j.amjopharm.2011.09.007. Epub 2011 Nov 4.
• Fonseca VA, Devries JH, Henry RR, Donsmark M, Thomsen HF, Plutzky J. Reductions in systolic blood pressure with liraglutide in patients with type 2 diabetes: insights from a patient-level pooled analysis of six randomized clinical trials. J Diabetes Complications. 2014 May-Jun;28(3):399-405. doi: 10.1016/j.jdiacomp.2014.01.009. Epub 2014 Jan 21.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: August 20, 2007
• First Submitted That Met QC Criteria: August 20, 2007
• First Posted (Estimate): August 21, 2007

Study Record Updates

• Last Update Posted (Actual): March 8, 2017
• Last Update Submitted That Met QC Criteria: January 25, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Liraglutide; Exenatide
• Other Study ID Numbers: NN2211-1797; 2006-006092-21 (EudraCT Number)