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

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”

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.

Intervention(s) in this Clinical Trial

• Drug: liraglutide
  • Stepwise dose increase, s.c. (under the skin) injection, once daily
• Drug: placebo
  • Liraglutide placebo, stepwise dose increase, s.c. (under the skin) injection, once daily
• Drug: glimepiride
  • Tablets, 1 - 4 mg daily

Arms, Groups and Cohorts in this Clinical Trial

• 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)
• 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)
• Active Comparator: Glimepiride
  • Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12

Primary Measures

• Change in Acetylcholine (ACh)-Mediated Forearm Blood Flow (FBF)
  • Time Frame: week 0, week 12
    Safety Issue?: No

Secondary Measures

• Change in Sodium Nitroprusside (SNP)-Mediated Forearm Blood Flow (FBF)
  • Time Frame: week 0, week 12
    Safety Issue?: No
• Change in HbA1c (Glycosylated Haemoglobin A1c)
  • Time Frame: week 0, week 12
    Safety Issue?: No
• Change in Fasting Plasma Glucose (FPG)
  • Time Frame: week 0, week 12
    Safety Issue?: No
• Change in Mean Postprandial Glucose (PPG) Based on Self-measured 7-point Plasma Glucose Profiles
  • Time Frame: week 0, week 12
    Safety Issue?: No
• Change in Body Weight
  • Time Frame: week 0, week 12
    Safety Issue?: No
• Fasting Lipid Profile - Change in Total Cholesterol (TC)
  • Time Frame: week 0, week 12
    Safety Issue?: No
• Fasting Lipid Profile - Change in LDL-C
  • Time Frame: week 0, week 12
    Safety Issue?: No
• Fasting Lipid Profile - Change in HDL-C
  • Time Frame: week 0, week 12
    Safety Issue?: No
• Fasting Lipid Profile - Change in Triglycerides (TG)
  • Time Frame: week 0, week 12
    Safety Issue?: No
• Biomarkers of Cardiovascular Risk - Change in TNF-alpha
  • Time Frame: week 0, week 12
    Safety Issue?: No
• Haematology and Biochemistry Tests - Number of Subjects With Blood Urea Nitrogen (BUN) Values Outside Reference Range
  • Time Frame: week 0, week 12
    Safety Issue?: Yes
• Haematology and Biochemistry Tests - Number of Subjects With Creatinine Values Outside Reference Range
  • Time Frame: week 0, week 12
    Safety Issue?: Yes
• Number of Hypoglycaemic Episodes
  • Time Frame: weeks 0-12
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Novo Nordisk Industry

Overall Clinical Trial Officials and Contacts

Jason Brett, MD Study Director Novo Nordisk  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00620282

Study ID Number: NN2211-1799

ClinicalTrials.gov Identifier: NCT00620282

Health Authority: United States: Institutional Review Board

Clinical Trials at Novo Nordisk