The Effect of Insulin Detemir in Combination With Liraglutide and Metformin Compared to Liraglutide and Metformin in Subjects With Type 2 Diabetes

Overview[ - collapse ][ - ]

Purpose This trial is conducted in Europe and North America. The aim of this clinical trial is to assess and compare the effect of insulin detemir in combination with liraglutide and metformin versus liraglutide and metformin in subjects with type 2 diabetes. Subjects will continue their own pre-trial metformin treatment during the trial.
ConditionDiabetes
Diabetes Mellitus, Type 2
InterventionDrug: liraglutide
Drug: insulin detemir
Drug: metformin
PhasePhase 3
SponsorNovo Nordisk A/S
Responsible PartyNovo Nordisk A/S
ClinicalTrials.gov IdentifierNCT00856986
First ReceivedMarch 5, 2009
Last UpdatedDecember 12, 2013
Last verifiedDecember 2013

Tracking Information[ + expand ][ + ]

First Received DateMarch 5, 2009
Last Updated DateDecember 12, 2013
Start DateMarch 2009
Estimated Primary Completion DateNovember 2010
Current Primary Outcome MeasuresMean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 26. [Time Frame: Week 0 (Randomisation), week 26] [Designated as safety issue: No]
Current Secondary Outcome Measures
  • Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 (for Intensified Subjects in Original Treatment Group) [Time Frame: Week 0, Week 52] [Designated as safety issue: No]
  • Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 (Values Before Intensification as LOCF) [Time Frame: Week 0, Week 52] [Designated as safety issue: No]
  • Mean Change From Randomisation in Fasting Plasma Glucose at Week 26 [Time Frame: Week 0 (Randomisation), Week 26] [Designated as safety issue: No]
  • Mean Change From Randomisation in Fasting Plasma Glucose at Week 52 [Time Frame: Week 0, Week 52] [Designated as safety issue: No]
  • Mean Change From Randomisation in 7-point Plasma Glucose Profile (Self-measured) at Week 26 [Time Frame: Week 0 (Randomisation), Week 26] [Designated as safety issue: No]Calculated as an estimate of the change in mean prandial increment of plasma glucose after breakfast, lunch and dinner (from baseline/randomisation (week 0) to 26 weeks), respectively. Prandial increments of plasma glucose were calculated as the difference between glucose values measured before and after each of these three meals, respectively.
  • Mean Change From Randomisation in 7-point Plasma Glucose Profile (Self-measured) at Week 52 [Time Frame: Week 0, Week 52] [Designated as safety issue: No]Calculated as an estimate of the change in mean prandial increment of plasma glucose after breakfast, lunch and dinner (from baseline (week 0) to 52 weeks), respectively. Prandial increments of plasma glucose were calculated as the difference between glucose values measured before and after each of these three meals, respectively.
  • Mean Change From Randomisation in Fasting Insulin at Week 26 [Time Frame: Week 0 (Randomisation), Week 26] [Designated as safety issue: No]
  • Mean Change From Randomisation in Fasting Insulin at Week 52 [Time Frame: Week 0 (Randomisation), Week 52] [Designated as safety issue: No]
  • Mean Change From Randomisation in Fasting Pro-insulin at Week 26. [Time Frame: Week 0 (Randomisation), Week 26] [Designated as safety issue: No]
  • Mean Change From Randomisation in Fasting Pro-insulin at Week 52 [Time Frame: Week 0, Week 52] [Designated as safety issue: No]
  • Mean Change From Randomisation in Fasting C-peptide at Week 26. [Time Frame: Week 0 (Randomisation), Week 26] [Designated as safety issue: No]
  • Mean Change From Randomisation in Fasting C-peptide at Week 52. [Time Frame: Week 0, Week 52] [Designated as safety issue: No]
  • Mean Changes From Randomisation in Cholesterol Lipids at Week 26. [Time Frame: Week 0 (Randomisation), Week 26] [Designated as safety issue: No]Cholesterol Lipids cover: Total Cholesterol, Low-density Lipoprotein Cholesterol (LDL-C), Very Low Density Lipoprotein Cholesterol (VLDL-C), High Density Lipoprotein Cholesterol (HDL-C)
  • Mean Changes From Randomisation in Cholesterol Lipids at Week 52. [Time Frame: Week 0, Week 52] [Designated as safety issue: No]Cholesterol Lipids cover: Total Cholesterol, Low-density Lipoprotein Cholesterol (LDL-C), Very Low Density Lipoprotein Cholesterol (VLDL-C), High Density Lipoprotein Cholesterol (HDL-C)
  • Mean Change From Randomisation in Lipids: Triglycerides at Week 26 [Time Frame: Week 0 (Randomisation), Week 26] [Designated as safety issue: No]
  • Mean Change From Randomisation in Lipids: Triglycerides at Week 52 [Time Frame: Week 0, Week 52] [Designated as safety issue: No]
  • Mean Change From Randomisation in Lipids: Free Fatty Acids (FFA) at Week 26 [Time Frame: Week 0 (Randomisation), Week 26] [Designated as safety issue: No]
  • Mean Change From Randomisation in Lipids: Free Fatty Acids (FFA) at Week 52 [Time Frame: Week 0, Week 52] [Designated as safety issue: No]
  • Mean Change From Randomisation in Body Weight at Week 26 [Time Frame: Week 0 (Randomisation), Week 26] [Designated as safety issue: No]
  • Mean Change From Randomisation in Body Weight at Week 52 [Time Frame: Week 0, Week 52] [Designated as safety issue: No]
  • Mean Change From Randomisation in Waist Circumference at Week 26. [Time Frame: Week 0 (Randomisation), Week 26] [Designated as safety issue: No]
  • Mean Change From Randomisation in Waist Circumference at Week 52. [Time Frame: Week 0, Week 52] [Designated as safety issue: No]
  • Mean Change From Randomisation in Hip Circumference at Week 26 [Time Frame: Week 0 (Randomisation), Week 26] [Designated as safety issue: No]
  • Mean Change From Randomisation in Hip Circumference at Week 52 [Time Frame: Week 0, week 52] [Designated as safety issue: No]
  • Mean Change From Randomisation in Waist to Hip Ratio at Week 26 [Time Frame: Week 0 (Randomisation), Week 26] [Designated as safety issue: No]Waist to Hip Ratio is calculated by dividing Waist circumference with Hip circumference
  • Mean Change From Randomisation in Waist to Hip Ratio at Week 52 [Time Frame: Week 0, Week 52] [Designated as safety issue: No]Waist to Hip Ratio is calculated by dividing Waist circumference with Hip circumference
  • Mean Change From Randomisation in Blood Pressure (Systolic and Diastolic) at Week 26. [Time Frame: Week 0 (Randomisation), Week 26] [Designated as safety issue: No]
  • Mean Change From Randomisation in Blood Pressure (Systolic and Diastolic) at Week 52. [Time Frame: Week 0, Week 52] [Designated as safety issue: No]
  • Adverse Events From Run-in (Week -12) to Week 52 [Time Frame: Run-in (week -12) to Week 52] [Designated as safety issue: No]
  • Hypoglycaemic Episodes (Excluding Outlier Subject), Weeks 0-26 [Time Frame: weeks 0-26] [Designated as safety issue: No]Number of hypoglycaemic episodes from Week 0 to Week 26, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.
  • Hypoglycaemic Episodes Weeks 0-52 [Time Frame: Week 0-52] [Designated as safety issue: No]Number of hypoglycaemic episodes from Week 0 to Week 52, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.

Descriptive Information[ + expand ][ + ]

Brief TitleThe Effect of Insulin Detemir in Combination With Liraglutide and Metformin Compared to Liraglutide and Metformin in Subjects With Type 2 Diabetes
Official TitleThe Effect of Insulin Detemir in Combination With Liraglutide and Metformin Compared to Liraglutide and Metformin in Subjects With Type 2 Diabetes. A 26 Week, Randomised, Open-label, Parallel-group, Multicentre, Multinational Trial With a 26 Week Extension
Brief Summary
This trial is conducted in Europe and North America. The aim of this clinical trial is to
assess and compare the effect of insulin detemir in combination with liraglutide and
metformin versus liraglutide and metformin in subjects with type 2 diabetes. Subjects will
continue their own pre-trial metformin treatment during the trial.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Diabetes
  • Diabetes Mellitus, Type 2
InterventionDrug: liraglutide
Liraglutide 1.8 mg/day for subcutaneous (under the skin) injection.
Drug: insulin detemir
Insulin detemir subcutaneous (under the skin) injection once daily. Dose will be titrated (individually adjusted) based on fasting self-measured plasma glucose levels according to a pre-specified algorithm
Drug: metformin
Metformin tablets, at least 1500 mg/day
Study Arm (s)
  • Experimental: Lira 1.8
    Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%
  • Experimental: Insulin detemir + Lira 1.8
    Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%
  • Experimental: Non-Randomised Lira 1.8
    Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%
  • Other: Early Withdrawals Lira 1.8
    Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial
  • Other: Intensified group
    Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment987
Estimated Completion DateNovember 2010
Estimated Primary Completion DateApril 2010
Eligibility Criteria
Inclusion Criteria:

- Subjects diagnosed with type 2 diabetes, insulin naïve and treated with metformin as
monotherapy for at least 3 months prior to screening, at a stable dose of at least
1500 mg/day or metformin (at least 1500 mg/day) and a sulfonylurea (less than or
equal to half of the maximum approved dose), both at a stable dose for at least 3
months prior to screening. Previous short-term insulin treatment in connection with
intercurrent illness is allowed at the discretion of the Investigator

- HbA1c 7.0-10.0% (both inclusive) for subjects on metformin monotherapy

- HbA1c 7.0-8.5% (both inclusive) for subjects on metformin in combination with a
sulphonylurea

Exclusion Criteria:

- Previous treatment with insulin (except for short-term treatment in connection with
intercurrent illness at the discretion of the Investigator)

- Treatment with glucose-lowering agent(s) other than stated in the inclusion criteria
in a period of 3 months prior to screening

- Recurrent major hypoglycaemia or hypoglycaemic unawareness as judged by the
Investigator

- Impaired kidney function

- Impaired liver function

- Uncontrolled treated/untreated hypertension

- Cancer or any clinically significant disease or disorder as judged by the
Investigator

- Previous participation in the run-in phase of this trial. Re-screening is allowed
once

- History of chronic pancreatitis or idiopathic pancreatitis
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States, Belgium, Canada, France, Germany, Italy, Netherlands, Spain, United Kingdom

Administrative Information[ + expand ][ + ]

NCT Number NCT00856986
Other Study ID NumbersNN2211-1842
Has Data Monitoring CommitteeNo
Information Provided ByNovo Nordisk A/S
Study SponsorNovo Nordisk A/S
CollaboratorsNot Provided
Investigators Study Director: Anne B. Thomsen, MD, PhD Novo Nordisk A/S
Verification DateDecember 2013

Locations[ + expand ][ + ]

Novo Nordisk Clinical Trial Call Center
Chino, California, United States, 91710
Novo Nordisk Clinical Trial Call Center
Fullerton, California, United States, 92835
Novo Nordisk Clinical Trial Call Center
Inglewood, California, United States, 9301-4106
Novo Nordisk Clinical Trial Call Center
La Jolla, California, United States, 92037
Novo Nordisk Clinical Trial Call Center
Los Gatos, California, United States, 95032
Novo Nordisk Clinical Trial Call Center
Spring Valley, California, United States, 91978
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Tustin, California, United States, 92780
Novo Nordisk Clinical Trial Call Center
Walnut Creek, California, United States, 94598
Novo Nordisk Clinical Trial Call Center
Waterbury, Connecticut, United States, 06712
Novo Nordisk Clinical Trial Call Center
Bradenton, Florida, United States, 34208
Novo Nordisk Clinical Trial Call Center
Clearwater, Florida, United States, 33765
Novo Nordisk Clinical Trial Call Center
Miami, Florida, United States, 33156
Novo Nordisk Clinical Trial Call Center
Miami, Florida, United States, 33136
Novo Nordisk Clinical Trial Call Center
Miami, Florida, United States, 33169
Novo Nordisk Clinical Trial Call Center
Atlanta, Georgia, United States, 30308-2253
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Decatur, Georgia, United States, 30033-9819
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Roswell, Georgia, United States, 30076
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Savannah, Georgia, United States, 31405
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Chicago, Illinois, United States, 60616
Novo Nordisk Clinical Trial Call Center
Quincy, Illinois, United States, 62301
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Louisville, Kentucky, United States, 40213
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Madisonville, Kentucky, United States, 42431
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Baltimore, Maryland, United States, 21204
Novo Nordisk Clinical Trial Call Center
Hyattsville, Maryland, United States, 20782
Novo Nordisk Clinical Trial Call Center
Rockville, Maryland, United States, 20852
Novo Nordisk Clinical Trial Call Center
Methuen, Massachusetts, United States, 01844
Novo Nordisk Clinical Trial Call Center
St. Louis, Missouri, United States, 63104
Novo Nordisk Clinical Trial Call Center
Bronx, New York, United States, 10461-2665
Novo Nordisk Clinical Trial Call Center
New Hyde Park, New York, United States, 11042
Novo Nordisk Clinical Trial Call Center
Northport, New York, United States, 11768
Novo Nordisk Clinical Trial Call Center
Charlotte, North Carolina, United States, 28277
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Durham, North Carolina, United States, 27710
Novo Nordisk Clinical Trial Call Center
Cincinnati, Ohio, United States, 45245
Novo Nordisk Clinical Trial Call Center
Cincinnati, Ohio, United States, 45226
Novo Nordisk Clinical Trial Call Center
Dayton, Ohio, United States, 45439
Novo Nordisk Clinical Trial Call Center
Oklahoma City, Oklahoma, United States, 73103
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Philadelphia, Pennsylvania, United States, 19152
Novo Nordisk Clinical Trial Call Center
State College, Pennsylvania, United States, 16801
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Willkes Barre, Pennsylvania, United States, 18711-3713
Novo Nordisk Clinical Trial Call Center
Chattanooga, Tennessee, United States, 37411
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Memphis, Tennessee, United States, 38119
Novo Nordisk Clinical Trial Call Center
Corpus Christi, Texas, United States, 78412
Novo Nordisk Clinical Trial Call Center
Dallas, Texas, United States, 75230
Novo Nordisk Clinical Trial Call Center
Dallas, Texas, United States, 75246
Novo Nordisk Clinical Trial Call Center
Dallas, Texas, United States, 75231
Novo Nordisk Clinical Trial Call Center
Dallas, Texas, United States, 75390-8858
Novo Nordisk Clinical Trial Call Center
Dallas, Texas, United States, 75235-6233
Novo Nordisk Clinical Trial Call Center
Midland, Texas, United States, 79707
Novo Nordisk Clinical Trial Call Center
Plano, Texas, United States, 75075
Novo Nordisk Clinical Trial Call Center
Orem, Utah, United States, 84058
Novo Nordisk Clinical Trial Call Center
Richmond, Virginia, United States, 23294
Novo Nordisk Clinical Trial Call Center
Richmond, Virginia, United States, 23249
Novo Nordisk Clinical Trial Call Center
Milwaukee, Wisconsin, United States, 53209
Belgium
Bonheiden, Belgium, 2820
Canada, Manitoba
Winnipeg, Manitoba, Canada, R3E 3P4
France
Paris Cedex 10, France, 75475
Germany
Frankfurt, Germany, 60388
Italy
Palermo, Italy, 90127
Netherlands
Doetinchem, Netherlands, 7001 GW
Novo Nordisk Clinical Trial Call Center
Bayamon, Puerto Rico, 00961
Novo Nordisk Clinical Trial Call Center
Carolina, Puerto Rico, 00983
Novo Nordisk Clinical Trial Call Center
Trujillo Alto, Puerto Rico, 00976
Spain
San Juan, Spain, 03550
United Kingdom
Bath, United Kingdom, BA1 2RG