The Effect of Liraglutide on Endothelial Function in Subjects With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00620282
First received: February 11, 2008
Last updated: August 30, 2012
Last verified: June 2012
  Purpose

This trial is conducted in the United States of America (USA). The purpose of the trial is to assess the effect of liraglutide on forearm blood flow in subjects with type 2 diabetes who are on diet and lifestyle changes or treated with metformin alone.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: The Effect of Liraglutide on Endothelial Function in Subjects With Type 2 Diabetes Mellitus: A 12-week Randomized, Double-blind, Placebo-controlled, Parallel-group, Single-center Trial With an Open-label Glimepiride Arm

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change in Acetylcholine (ACh)-Mediated Forearm Blood Flow (FBF) [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
    Assessed endothelial function by measuring the change in ACh-mediated FBF at euglycemia (90 mg/dL) using forearm venous occlusion plethysmography (VOP) technique. Unit of Measure refers to volume of blood (mL) per 100 mL of forearm tissue per minute.


Secondary Outcome Measures:
  • Change in Sodium Nitroprusside (SNP)-Mediated Forearm Blood Flow (FBF) [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
    Assessed endothelial function by measuring the change in SNP-mediated FBF at euglycemia (90 mg/dL) using forearm venous occlusion plethysmography (VOP) technique. Unit of Measure refers to volume of blood (mL) per 100 mL of forearm tissue per minute.

  • Change in HbA1c (Glycosylated Haemoglobin A1c) [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
    Percentage point change in HbA1c

  • Change in Fasting Plasma Glucose (FPG) [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
    Change in FPG

  • Change in Mean Postprandial Glucose (PPG) Based on Self-measured 7-point Plasma Glucose Profiles [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
    The 7-point profile included plasma glucose measurements at the following time points: before each main meal (breakfast, lunch and dinner), 90 minutes after the start of each main meal (breakfast, lunch and dinner) and at bedtime.

  • Change in Body Weight [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
  • Fasting Lipid Profile - Change in Total Cholesterol (TC) [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
    Change in TC

  • Fasting Lipid Profile - Change in LDL-C [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
    Change in LDL-C

  • Fasting Lipid Profile - Change in HDL-C [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
    Change in HDL-C

  • Fasting Lipid Profile - Change in Triglycerides (TG) [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
    Change in TG

  • Biomarkers of Cardiovascular Risk - Change in TNF-alpha [ Time Frame: week 0, week 12 ] [ Designated as safety issue: No ]
    Change in TNF-alpha

  • Haematology and Biochemistry Tests - Number of Subjects With Blood Urea Nitrogen (BUN) Values Outside Reference Range [ Time Frame: week 0, week 12 ] [ Designated as safety issue: Yes ]
    Number of subjects with serum BUN values outside reference range at Week 0 and Week 12, respectively. Reference range: Female (lower value 6.000 mg/dL, upper value 21.000 mg/dL) Male (lower value 8.000 mg/dL, upper value 25.000 mg/dL).

  • Haematology and Biochemistry Tests - Number of Subjects With Creatinine Values Outside Reference Range [ Time Frame: week 0, week 12 ] [ Designated as safety issue: Yes ]
    Number of subjects with serum creatinine values outside reference range at Week 0 and Week 12, respectively. Reference range: Female (lower value 0.600 mg/dL, upper value 1.100 mg/dL) Male (lower value 0.800 mg/dL, upper value 1.300 mg/dL).

  • Number of Hypoglycaemic Episodes [ Time Frame: weeks 0-12 ] [ Designated as safety issue: Yes ]
    Total number of hypoglycaemic episodes occurring from week 0 to week 12. Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself and either plasma glucose was below 56 mg/dL or symptoms were reversed after food intake or glucagon/intravenous glucose administration. Minor if subject was able to treat her/himself and plasma glucose was below 56 mg/dL. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 56 mg/dL.


Enrollment: 49
Study Start Date: February 2008
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lira 1.8
Liraglutide 1.8 mg administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12)
Drug: liraglutide
Stepwise dose increase, s.c. (under the skin) injection, once daily
Placebo Comparator: Placebo
Placebo administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12)
Drug: placebo
Liraglutide placebo, stepwise dose increase, s.c. (under the skin) injection, once daily
Active Comparator: Glimepiride
Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12
Drug: glimepiride
Tablets, 1 - 4 mg daily

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 diabetes
  • Diet and lifestyle changes or metformin monotherapy for at least three months
  • HbA1c (glycosylated haemoglobin) 6.5-9.0% (both inclusive)
  • Body Mass Index (BMI) less than or equal to 40 kg/m^2

Exclusion Criteria:

  • Previous treatment with insulin (except for short term treatment with insulin in connection with intercurrent illness, at the discretion of the Investigator)
  • Previous treatment with glucagon-like peptide-1 (GLP-1) analogues/mimetics, including treatment in a clinical trial
  • Treatment with any oral hypoglycaemic agents other than metformin in a period of 3 months prior to screening
  • Current smoker or history of smoking within 6 months prior to screening
  • Evidence of overt cardiovascular disease (documented coronary heart disease, class II-IV congestive heart failure, cerebrovascular disease, or peripheral vascular disease)
  • Abnormal, clinically significant exercise stress electrocardiogram (ECG) test, as judged by the Investigator
  • Known retinopathy or maculopathy requiring acute treatment, as judged by the Investigator
  • Known autonomic neuropathy, as judged by the Investigator
  • Initiation or change (dose or treatment regimen) in concomitant blood pressure-lowering or lipid-lowering medication within 4 weeks prior to screening
  • Systolic blood pressure more than or equal to 140 mmHg and/or diastolic blood pressure more than or equal to 90 mmHg
  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: NCT00620282

Locations
United States, Minnesota
Novo Nordisk Clinical Trial Call Center
Rochester, Minnesota, United States, 55905-0001
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Jason Brett, MD Novo Nordisk A/S
  More Information

Additional Information:
No publications provided

Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00620282     History of Changes
Other Study ID Numbers: NN2211-1799
Study First Received: February 11, 2008
Results First Received: May 19, 2011
Last Updated: August 30, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glimepiride
Liraglutide
Glucagon-Like Peptide 1
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on August 21, 2014