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

Diabetes Mellitus, Type 2 Clinical Trial

— LEAD-6  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00518882
• Other study ID #: NN2211-1797
• Secondary ID: 2006-006092-21
• Status: Completed
• Phase: Phase 3
• First received: August 20, 2007
• Last updated: November 13, 2014
• Start date: August 2007
• Est. completion date: April 2009

Study information

• Verified date: November 2014
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationFinland: Finnish Medicines AgencySwitzerland: SwissmedicGermany: Federal Institute for Drugs and Medical DevicesIreland: Irish Medicines BoardAustria: Federal Ministry for Health and WomenPoland: The Office for Registration of Medicinal Products, Medical Devices; and Biocides, Central Evidence of Clinical TrialsDenmark: Danish Medicines AgencyMacedonia, The Former Yugoslav Republic of: Drug Agency, Ministry of HealthSlovenia: Agency of Drugs and Medicinal Products of the Slovenian RepublicRomania: National Medicines AgencySweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 467
• Est. completion date: April 2009
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• liraglutide
1.8 mg once daily for s.c. (under the skin) injection.
• exenatide
10 mcg twice daily for s.c. (under the skin) injection.

Locations

Country	Name	City	State
Puerto Rico	Novo Nordisk Clinical Trial Call Center	Manati
United States	Novo Nordisk Clinical Trial Call Center	Artesia	California
United States	Novo Nordisk Clinical Trial Call Center	Atlanta	Georgia
United States	Novo Nordisk Clinical Trial Call Center	Austin	Texas
United States	Novo Nordisk Clinical Trial Call Center	Birmingham	Alabama
United States	Novo Nordisk Clinical Trial Call Center	Canton	Ohio
United States	Novo Nordisk Clinical Trial Call Center	Chattanooga	Tennessee
United States	Novo Nordisk Clinical Trial Call Center	Chicago	Illinois
United States	Novo Nordisk Clinical Trial Call Center	Cincinnati	Ohio
United States	Novo Nordisk Clinical Trial Call Center	Corpus Christi	Texas
United States	Novo Nordisk Clinical Trial Call Center	Dallas	Texas
United States	Novo Nordisk Clinical Trial Call Center	Dayton	Ohio
United States	Novo Nordisk Clinical Trial Call Center	Des Moines	Iowa
United States	Novo Nordisk Clinical Trial Call Center	Durham	North Carolina
United States	Novo Nordisk Clinical Trial Call Center	Escondido	California
United States	Novo Nordisk Clinical Trial Call Center	Evansville	Indiana
United States	Novo Nordisk Clinical Trial Call Center	Flemington	New Jersey
United States	Novo Nordisk Clinical Trial Call Center	Goodyear	Arizona
United States	Novo Nordisk Clinical Trial Call Center	Hollywood	Florida
United States	Novo Nordisk Clinical Trial Call Center	Houston	Texas
United States	Novo Nordisk Clinical Trial Call Center	Idaho Falls	Idaho
United States	Novo Nordisk Clinical Trial Call Center	Jacksonville	Florida
United States	Novo Nordisk Clinical Trial Call Center	Longwood	Florida
United States	Novo Nordisk Clinical Trial Call Center	Mentor	Ohio
United States	Novo Nordisk Clinical Trial Call Center	Midland	Texas
United States	Novo Nordisk Clinical Trial Call Center	Milwaukee	Wisconsin
United States	Novo Nordisk Clinical Trial Call Center	Minneapolis	Minnesota
United States	Novo Nordisk Clinical Trial Call Center	Norfolk	Virginia
United States	Novo Nordisk Clinical Trial Call Center	Northport	New York
United States	Novo Nordisk Clinical Trial Call Center	Ocala	Florida
United States	Novo Nordisk Clinical Trial Call Center	Olympia	Washington
United States	Novo Nordisk Clinical Trial Call Center	Orange	California
United States	Novo Nordisk Clinical Trial Call Center	Peoria	Illinois
United States	Novo Nordisk Clinical Trial Call Center	Philadelphia	Pennsylvania
United States	Novo Nordisk Clinical Trial Call Center	Plantation	Florida
United States	Novo Nordisk Clinical Trial Call Center	Richmond	Virginia
United States	Novo Nordisk Clinical Trial Call Center	Roswell	Georgia
United States	Novo Nordisk Clinical Trial Call Center	Sacramento	California
United States	Novo Nordisk Clinical Trial Call Center	San Antonio	Texas
United States	Novo Nordisk Clinical Trial Call Center	San Mateo	California
United States	Novo Nordisk Clinical Trial Call Center	Spokane	Washington
United States	Novo Nordisk Clinical Trial Call Center	Spring Valley	California
United States	Novo Nordisk Clinical Trial Call Center	St. Cloud	Florida
United States	Novo Nordisk Clinical Trial Call Center	St. Peters	Missouri
United States	Novo Nordisk Clinical Trial Call Center	Sumter	South Carolina
United States	Novo Nordisk Clinical Trial Call Center	Tipton	Pennsylvania
United States	Novo Nordisk Clinical Trial Call Center	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Austria,  Denmark,  Finland,  France,  Germany,  Ireland,  Macedonia, The Former Yugoslav Republic of,  Norway,  Poland,  Puerto Rico,  Romania,  Slovenia,  Spain,  Sweden,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes

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