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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00856986
First received: March 5, 2009
Last updated: December 12, 2013
Last verified: December 2013
  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.


Condition Intervention Phase
Diabetes
Diabetes Mellitus, Type 2
Drug: liraglutide
Drug: insulin detemir
Drug: metformin
Phase 3

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 26. [ Time Frame: Week 0 (Randomisation), week 26 ] [ Designated as safety issue: No ]

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.


Enrollment: 987
Study Start Date: March 2009
Study Completion Date: November 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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%
Drug: liraglutide
Liraglutide 1.8 mg/day for subcutaneous (under the skin) injection.
Drug: metformin
Metformin tablets, at least 1500 mg/day
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%
Drug: 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
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%
Drug: liraglutide
Liraglutide 1.8 mg/day for subcutaneous (under the skin) injection.
Drug: metformin
Metformin tablets, at least 1500 mg/day
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
Drug: liraglutide
Liraglutide 1.8 mg/day for subcutaneous (under the skin) injection.
Drug: metformin
Metformin tablets, at least 1500 mg/day
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.
Drug: 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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00856986

  Show 64 Study Locations
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Anne B. Thomsen, 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: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00856986     History of Changes
Other Study ID Numbers: NN2211-1842, 2007-005317-19
Study First Received: March 5, 2009
Results First Received: April 19, 2011
Last Updated: December 12, 2013
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Netherlands: Medicines Evaluation Board, Dutch Health Care Inspectorate
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Liraglutide
Insulin
Metformin
Insulin, Long-Acting
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 August 21, 2014