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

Phase 3

Completed

Conditions: Diabetes
Diabetes Mellitus, Type 2

Interventions: Drug: placebo
Drug: liraglutide
Drug: glimepiride

Registration Number: NCT00620282

Lead Sponsor: Novo Nordisk A/S

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 49

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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)
Lira 1.8	liraglutide	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)
Glimepiride	glimepiride	Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12

Primary Outcome Measures

Name	Time	Method
Change in Acetylcholine (ACh)-Mediated Forearm Blood Flow (FBF)	week 0, week 12	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

Name	Time	Method
Change in HbA1c (Glycosylated Haemoglobin A1c)	week 0, week 12	Percentage point change in HbA1c
Number of Hypoglycaemic Episodes	weeks 0-12	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.
Change in Sodium Nitroprusside (SNP)-Mediated Forearm Blood Flow (FBF)	week 0, week 12	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 Fasting Plasma Glucose (FPG)	week 0, week 12	Change in FPG
Fasting Lipid Profile - Change in Total Cholesterol (TC)	week 0, week 12	Change in TC
Biomarkers of Cardiovascular Risk - Change in TNF-alpha	week 0, week 12	Change in TNF-alpha
Haematology and Biochemistry Tests - Number of Subjects With Blood Urea Nitrogen (BUN) Values Outside Reference Range	week 0, week 12	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	week 0, week 12	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).
Change in Mean Postprandial Glucose (PPG) Based on Self-measured 7-point Plasma Glucose Profiles	week 0, week 12	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	week 0, week 12
Fasting Lipid Profile - Change in LDL-C	week 0, week 12	Change in LDL-C
Fasting Lipid Profile - Change in HDL-C	week 0, week 12	Change in HDL-C
Fasting Lipid Profile - Change in Triglycerides (TG)	week 0, week 12	Change in TG