The Effect of Liraglutide on Endothelial Function in Subjects With Type 2 Diabetes Mellitus
Sponsor
Novo Nordisk A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT00620282
Collaborator
(none)
49
1
3
26.9
1.8
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
49 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, 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
Study Start Date
:
Feb 1, 2008
Actual Primary Completion Date
:
May 1, 2010
Actual Study Completion Date
:
May 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 HbA1c (Glycosylated Haemoglobin A1c) [week 0, week 12]
Percentage point change in HbA1c
- Change in Fasting Plasma Glucose (FPG) [week 0, week 12]
Change in FPG
- 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 Total Cholesterol (TC) [week 0, week 12]
Change in TC
- 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
- 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).
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
40 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novo Nordisk Investigational Site | Rochester | Minnesota | United States | 55905 |
Sponsors and Collaborators
- Novo Nordisk A/S
Investigators
- Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00620282
Other Study ID Numbers:
- NN2211-1799
First Posted:
Feb 21, 2008
Last Update Posted:
Mar 8, 2017
Last Verified:
Jan 1, 2017
Study Results
Participant Flow
| Recruitment Details | The trial was conducted at one site in the United States of America (USA). |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride |
|---|---|---|---|
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 |
| Period Title: Overall Study | |||
| STARTED | 16 | 16 | 17 |
| COMPLETED | 16 | 14 | 16 |
| NOT COMPLETED | 0 | 2 | 1 |
Baseline Characteristics
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride | Total |
|---|---|---|---|---|
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 | Total of all reporting groups |
| Overall Participants | 16 | 16 | 17 | 49 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
57.7
(9.0)
|
60.3
(7.3)
|
57.7
(5.3)
|
58.5
(7.3)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
6
37.5%
|
6
37.5%
|
6
35.3%
|
18
36.7%
|
| Male |
10
62.5%
|
10
62.5%
|
11
64.7%
|
31
63.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
16
100%
|
16
100%
|
17
100%
|
49
100%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
16
100%
|
16
100%
|
17
100%
|
49
100%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Duration of Diabetes (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
5.3
(4.1)
|
8.4
(4.6)
|
6.8
(8.1)
|
6.8
(6.0)
|
| Previous Anti-diabetic Treatment (participants) [Number] | ||||
| Diet/Exercise |
2
12.5%
|
1
6.3%
|
2
11.8%
|
5
10.2%
|
| Metformin |
14
87.5%
|
15
93.8%
|
15
88.2%
|
44
89.8%
|
| Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kg/m^2] |
32.7
(4.5)
|
31.6
(4.2)
|
31.1
(4.9)
|
31.8
(4.5)
|
| Body Weight (kg) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kg] |
95.09
(13.12)
|
90.63
(13.47)
|
91.99
(13.97)
|
92.56
(13.38)
|
| Glycosylated Haemoglobin A1c (HbA1c) (percentage of total haemoglobin) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [percentage of total haemoglobin] |
7.2
(0.5)
|
7.0
(0.5)
|
7.3
(0.5)
|
7.2
(0.5)
|
| Fasting Plasma Glucose (FPG) (mg/dL) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [mg/dL] |
160.8
(31.2)
|
145.2
(20.1)
|
163.3
(33.3)
|
156.6
(29.4)
|
| Total Cholesterol (TC) (mg/dL) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [mg/dL] |
170.2
(34.4)
|
157.5
(32.0)
|
160.2
(24.1)
|
162.6
(30.2)
|
| Low density lipoprotein (LDL-C) (mg/dL) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [mg/dL] |
102.8
(31.3)
|
92.5
(23.5)
|
94.1
(18.4)
|
96.4
(24.8)
|
| High density lipoprotein (HDL-C) (mg/dL) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [mg/dL] |
39.6
(10.0)
|
39.2
(7.5)
|
43.5
(10.3)
|
40.8
(9.4)
|
| Triglycerides (TG) (mg/dL) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [mg/dL] |
165.8
(72.9)
|
145.9
(57.5)
|
141.4
(67.4)
|
150.8
(65.7)
|
| Tumor necrosis factor-alpha (TNF-alpha) (pg/mL) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [pg/mL] |
2.1
(1.5)
|
1.4
(0.8)
|
1.4
(0.5)
|
1.6
(1.0)
|
Outcome Measures
| Title | Change in Acetylcholine (ACh)-Mediated Forearm Blood Flow (FBF) |
|---|---|
| Description | 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. |
| Time Frame | week 0, week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial. |
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride |
|---|---|---|---|
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 |
| Measure Participants | 16 | 14 | 16 |
| Least Squares Mean (Standard Error) [mL/100 mL/min] |
4.244
(2.551)
|
-3.187
(2.758)
|
2.164
(2.568)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Placebo |
|---|---|---|
| Comments | Change in Ach-mediated FBF from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline FBF as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0549 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | 7.43 | |
| Confidence Interval |
() 95% -0.164 to 15.025 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Glimepiride |
|---|---|---|
| Comments | Change in Ach-mediated FBF from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline FBF as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5681 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | 2.08 | |
| Confidence Interval |
() 95% -5.215 to 9.375 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Glimepiride |
|---|---|---|
| Comments | Change in Ach-mediated FBF from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline FBF as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1668 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | 5.35 | |
| Confidence Interval |
() 95% -2.323 to 13.024 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Sodium Nitroprusside (SNP)-Mediated Forearm Blood Flow (FBF) |
|---|---|
| Description | 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. |
| Time Frame | week 0, week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial. |
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride |
|---|---|---|---|
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 |
| Measure Participants | 16 | 14 | 16 |
| Least Squares Mean (Standard Error) [mL/100 mL/min] |
3.455
(2.681)
|
-1.044
(2.893)
|
2.746
(2.67)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Placebo |
|---|---|---|
| Comments | Change in SNP-mediated FBF from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline FBF as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2648 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | 4.499 | |
| Confidence Interval |
() 95% -3.535 to 12.534 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Glimepiride |
|---|---|---|
| Comments | Change in SNP-mediated FBF from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline FBF as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8518 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | 0.709 | |
| Confidence Interval |
() 95% -6.904 to 8.322 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Glimepiride |
|---|---|---|
| Comments | Change in SNP-mediated FBF from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline FBF as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3435 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | 3.79 | |
| Confidence Interval |
() 95% -4.194 to 11.774 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in HbA1c (Glycosylated Haemoglobin A1c) |
|---|---|
| Description | Percentage point change in HbA1c |
| Time Frame | week 0, week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial. |
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride |
|---|---|---|---|
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 |
| Measure Participants | 16 | 14 | 16 |
| Least Squares Mean (Standard Error) [percentage of total haemoglobin] |
-0.629
(0.109)
|
-0.094
(0.121)
|
-0.552
(0.112)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Placebo |
|---|---|---|
| Comments | Change in HbA1c from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline HbA1c as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0023 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -0.536 | |
| Confidence Interval |
() 95% -0.868 to -0.203 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Glimepiride |
|---|---|---|
| Comments | Change in HbA1c from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline HbA1c as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6207 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -0.077 | |
| Confidence Interval |
() 95% -0.391 to 0.236 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Glimepiride |
|---|---|---|
| Comments | Change in HbA1c from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline HbA1c as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0098 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -0.458 | |
| Confidence Interval |
() 95% -0.8 to -0.116 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Fasting Plasma Glucose (FPG) |
|---|---|
| Description | Change in FPG |
| Time Frame | week 0, week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial. |
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride |
|---|---|---|---|
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 |
| Measure Participants | 16 | 14 | 16 |
| Least Squares Mean (Standard Error) [mg/dL] |
-41.672
(3.643)
|
-6.067
(4.079)
|
-32.019
(3.708)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Placebo |
|---|---|---|
| Comments | Change in FPG from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline FPG as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -35.605 | |
| Confidence Interval |
() 95% -46.797 to -24.413 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Glimepiride |
|---|---|---|
| Comments | Change in FPG from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline FPG as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0677 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -9.653 | |
| Confidence Interval |
() 95% -20.041 to 0.736 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Glimepiride |
|---|---|---|
| Comments | Change in FPG from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline FPG as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -25.952 | |
| Confidence Interval |
() 95% -37.429 to -14.475 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Mean Postprandial Glucose (PPG) Based on Self-measured 7-point Plasma Glucose Profiles |
|---|---|
| Description | 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. |
| Time Frame | week 0, week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial. |
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride |
|---|---|---|---|
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 |
| Measure Participants | 13 | 10 | 14 |
| Least Squares Mean (Standard Error) [mg/dL] |
-32.175
(9.104)
|
-20.304
(10.619)
|
-35.99
(8.673)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Placebo |
|---|---|---|
| Comments | Change in PPG from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline PPG as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4121 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -11.871 | |
| Confidence Interval |
() 95% -40.943 to 17.201 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Glimepiride |
|---|---|---|
| Comments | Change in PPG from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline PPG as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7622 |
| Comments | 2-sided significance level of 5% | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | 3.815 | |
| Confidence Interval |
() 95% -21.618 to 29.247 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Glimepiride |
|---|---|---|
| Comments | Change in PPG from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline PPG as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2651 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -15.686 | |
| Confidence Interval |
() 95% -43.838 to 12.466 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Body Weight |
|---|---|
| Description | |
| Time Frame | week 0, week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial. |
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride |
|---|---|---|---|
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 |
| Measure Participants | 16 | 14 | 17 |
| Least Squares Mean (Standard Error) [kg] |
-1.821
(0.455)
|
-0.293
(0.486)
|
1.038
(0.441)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Placebo |
|---|---|---|
| Comments | Change in body weight from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline body weight as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0268 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -1.528 | |
| Confidence Interval |
() 95% -2.873 to -0.184 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Glimepiride |
|---|---|---|
| Comments | Change in body weight from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline body weight as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -2.859 | |
| Confidence Interval |
() 95% -4.139 to -1.579 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Glimepiride |
|---|---|---|
| Comments | Change in body weight from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline body weight as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0486 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | 1.331 | |
| Confidence Interval |
() 95% 0.0090 to 2.653 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Fasting Lipid Profile - Change in Total Cholesterol (TC) |
|---|---|
| Description | Change in TC |
| Time Frame | week 0, week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial. |
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride |
|---|---|---|---|
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 |
| Measure Participants | 16 | 14 | 16 |
| Least Squares Mean (Standard Error) [mg/dL] |
2.006
(5.274)
|
4.243
(5.597)
|
0.094
(5.239)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Placebo |
|---|---|---|
| Comments | Change in TC from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline TC as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7736 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -2.237 | |
| Confidence Interval |
() 95% -17.829 to 13.354 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Glimepiride |
|---|---|---|
| Comments | Change in TC from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline TC as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7993 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | 1.912 | |
| Confidence Interval |
() 95% -13.168 to 16.991 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Glimepiride |
|---|---|---|
| Comments | Change in TC from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline TC as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5903 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -4.149 | |
| Confidence Interval |
() 95% -19.582 to 11.284 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Fasting Lipid Profile - Change in LDL-C |
|---|---|
| Description | Change in LDL-C |
| Time Frame | week 0, week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial. |
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride |
|---|---|---|---|
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 |
| Measure Participants | 16 | 14 | 16 |
| Least Squares Mean (Standard Error) [mg/dL] |
1.243
(4.294)
|
-2.459
(4.551)
|
-1.529
(4.275)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Placebo |
|---|---|---|
| Comments | Change in LDL-C from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline LDL-C as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5583 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | 3.702 | |
| Confidence Interval |
() 95% -8.96 to 16.365 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Glimepiride |
|---|---|---|
| Comments | Change in LDL-C from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline LDL-C as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6517 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | 2.773 | |
| Confidence Interval |
() 95% -9.537 to 15.082 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Glimepiride |
|---|---|---|
| Comments | Change in LDL-C from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline LDL-C as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8822 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | 0.929 | |
| Confidence Interval |
() 95% -11.646 to 13.505 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Fasting Lipid Profile - Change in HDL-C |
|---|---|
| Description | Change in HDL-C |
| Time Frame | week 0, week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial. |
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride |
|---|---|---|---|
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 |
| Measure Participants | 16 | 14 | 16 |
| Least Squares Mean (Standard Error) [mg/dL] |
0.393
(1.053)
|
0.562
(1.133)
|
1.116
(1.074)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Placebo |
|---|---|---|
| Comments | Change in HDL-C from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline HDL-C as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9131 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -0.169 | |
| Confidence Interval |
() 95% -3.273 to 2.935 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Glimepiride |
|---|---|---|
| Comments | Change in HDL-C from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline HDL-C as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6362 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -0.723 | |
| Confidence Interval |
() 95% -3.785 to 2.339 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Glimepiride |
|---|---|---|
| Comments | Change in HDL-C from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline HDL-C as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7283 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | 0.554 | |
| Confidence Interval |
() 95% -2.643 to 3.751 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Fasting Lipid Profile - Change in Triglycerides (TG) |
|---|---|
| Description | Change in TG |
| Time Frame | week 0, week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial. |
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride |
|---|---|---|---|
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 |
| Measure Participants | 16 | 14 | 16 |
| Least Squares Mean (Standard Error) [mg/dL] |
-8.163
(13.471)
|
28.546
(14.282)
|
-4.377
(13.399)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Placebo |
|---|---|---|
| Comments | Change in TG from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline TG as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0694 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -36.709 | |
| Confidence Interval |
() 95% -76.467 to 3.048 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Glimepiride |
|---|---|---|
| Comments | Change in TG from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline TG as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.844 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -3.786 | |
| Confidence Interval |
() 95% -42.373 to 34.801 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Glimepiride |
|---|---|---|
| Comments | Change in TG from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline TG as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0994 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -32.923 | |
| Confidence Interval |
() 95% -72.353 to 6.507 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Biomarkers of Cardiovascular Risk - Change in TNF-alpha |
|---|---|
| Description | Change in TNF-alpha |
| Time Frame | week 0, week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial. |
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride |
|---|---|---|---|
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 |
| Measure Participants | 12 | 10 | 12 |
| Least Squares Mean (Standard Error) [pg/mL] |
-0.024
(0.232)
|
0.397
(0.25)
|
-0.0050
(0.231)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Placebo |
|---|---|---|
| Comments | Change in TNF-alpha from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline TNF-alpha as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2282 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -0.42 | |
| Confidence Interval |
() 95% -1.118 to 0.278 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Lira 1.8, Glimepiride |
|---|---|---|
| Comments | Change in TNF-alpha from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline TNF-alpha as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9569 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -0.018 | |
| Confidence Interval |
() 95% -0.697 to 0.661 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Glimepiride |
|---|---|---|
| Comments | Change in TNF-alpha from baseline to end of treatment at 12 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline TNF-alpha as a covariate. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2465 |
| Comments | 2-sided significance level of 5%. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares mean |
| Estimated Value | -0.402 | |
| Confidence Interval |
() 95% -1.097 to 0.293 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Haematology and Biochemistry Tests - Number of Subjects With Blood Urea Nitrogen (BUN) Values Outside Reference Range |
|---|---|
| Description | 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). |
| Time Frame | week 0, week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all subjects exposed to at least one dose of the drug or who underwent at least one venous occlusion plethysmography (VOP) procedure. |
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride |
|---|---|---|---|
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 |
| Measure Participants | 16 | 16 | 17 |
| Week 0 |
1
6.3%
|
0
0%
|
1
5.9%
|
| Week 12 |
1
6.3%
|
2
12.5%
|
0
0%
|
| Title | Haematology and Biochemistry Tests - Number of Subjects With Creatinine Values Outside Reference Range |
|---|---|
| Description | 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). |
| Time Frame | week 0, week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all subjects exposed to at least one dose of the drug or who underwent at least one venous occlusion plethysmography (VOP) procedure. |
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride |
|---|---|---|---|
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 |
| Measure Participants | 16 | 16 | 17 |
| Week 0 |
1
6.3%
|
3
18.8%
|
5
29.4%
|
| Week 12 |
1
6.3%
|
2
12.5%
|
2
11.8%
|
| Title | Number of Hypoglycaemic Episodes |
|---|---|
| Description | 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. |
| Time Frame | weeks 0-12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all subjects exposed to at least one dose of the drug or who underwent at least one venous occlusion plethysmography (VOP) procedure. |
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride |
|---|---|---|---|
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 |
| Measure Participants | 16 | 16 | 17 |
| Major |
0
|
0
|
0
|
| Minor |
1
|
0
|
10
|
| Symptoms Only |
3
|
0
|
4
|
Adverse Events
| Time Frame | The adverse events were collected from week 0 to week 12. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The full safety analysis set is all subjects exposed to at least one dose of the drug or who underwent at least one venous occlusion plethysmography (VOP) procedure. | |||||
| Arm/Group Title | Lira 1.8 | Placebo | Glimepiride | |||
| Arm/Group Description | 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 administered subcutaneously, once-daily, weeks 0-12 (100 uL/day, week 1; 200 uL/day, week 2; 300 uL/day, week 3-12) | Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 | |||
All Cause Mortality |
||||||
| Lira 1.8 | Placebo | Glimepiride | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Lira 1.8 | Placebo | Glimepiride | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/16 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Prostate Cancer | 0/16 (0%) | 0 | 1/16 (6.3%) | 1 | 0/17 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Lira 1.8 | Placebo | Glimepiride | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/16 (68.8%) | 9/16 (56.3%) | 5/17 (29.4%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain upper | 1/16 (6.3%) | 1 | 0/16 (0%) | 0 | 0/17 (0%) | 0 |
| Diarrhoea | 1/16 (6.3%) | 1 | 0/16 (0%) | 0 | 0/17 (0%) | 0 |
| Dyspepsia | 2/16 (12.5%) | 2 | 0/16 (0%) | 0 | 0/17 (0%) | 0 |
| Nausea | 2/16 (12.5%) | 2 | 0/16 (0%) | 0 | 0/17 (0%) | 0 |
| Parotid Duct Obstruction | 1/16 (6.3%) | 1 | 0/16 (0%) | 0 | 0/17 (0%) | 0 |
| Vomiting | 2/16 (12.5%) | 2 | 0/16 (0%) | 0 | 0/17 (0%) | 0 |
| General disorders | ||||||
| Catheter Site Haematoma | 0/16 (0%) | 0 | 0/16 (0%) | 0 | 1/17 (5.9%) | 1 |
| Chest Pain | 0/16 (0%) | 0 | 1/16 (6.3%) | 1 | 0/17 (0%) | 0 |
| Fatigue | 0/16 (0%) | 0 | 1/16 (6.3%) | 1 | 0/17 (0%) | 0 |
| Oedema peripheral | 1/16 (6.3%) | 1 | 0/16 (0%) | 0 | 0/17 (0%) | 0 |
| Infections and infestations | ||||||
| Bronchitis | 0/16 (0%) | 0 | 1/16 (6.3%) | 1 | 0/17 (0%) | 0 |
| Gastroenteritis viral | 1/16 (6.3%) | 1 | 0/16 (0%) | 0 | 0/17 (0%) | 0 |
| Influenza | 0/16 (0%) | 0 | 0/16 (0%) | 0 | 1/17 (5.9%) | 1 |
| Nasopharyngitis | 0/16 (0%) | 0 | 0/16 (0%) | 0 | 1/17 (5.9%) | 1 |
| Otitis media | 0/16 (0%) | 0 | 1/16 (6.3%) | 1 | 0/17 (0%) | 0 |
| Sinusitis | 1/16 (6.3%) | 1 | 0/16 (0%) | 0 | 0/17 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Arthropod Bite | 1/16 (6.3%) | 1 | 0/16 (0%) | 0 | 0/17 (0%) | 0 |
| Back Injury | 0/16 (0%) | 0 | 1/16 (6.3%) | 1 | 0/17 (0%) | 0 |
| Fall | 1/16 (6.3%) | 1 | 0/16 (0%) | 0 | 0/17 (0%) | 0 |
| Head Injury | 1/16 (6.3%) | 1 | 0/16 (0%) | 0 | 0/17 (0%) | 0 |
| Joint dislocation | 0/16 (0%) | 0 | 1/16 (6.3%) | 1 | 0/17 (0%) | 0 |
| Procedural Pain | 0/16 (0%) | 0 | 1/16 (6.3%) | 1 | 0/17 (0%) | 0 |
| Skin laceration | 1/16 (6.3%) | 1 | 0/16 (0%) | 0 | 0/17 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 1/16 (6.3%) | 1 | 0/16 (0%) | 0 | 0/17 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/16 (0%) | 0 | 0/16 (0%) | 0 | 1/17 (5.9%) | 1 |
| Back Pain | 0/16 (0%) | 0 | 0/16 (0%) | 0 | 1/17 (5.9%) | 1 |
| Muscle Disorder | 0/16 (0%) | 0 | 0/16 (0%) | 0 | 1/17 (5.9%) | 1 |
| Musculoskeletal pain | 1/16 (6.3%) | 1 | 0/16 (0%) | 0 | 0/17 (0%) | 0 |
| Pain In Extremity | 0/16 (0%) | 0 | 1/16 (6.3%) | 1 | 0/17 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Prostate Cancer | 0/16 (0%) | 0 | 1/16 (6.3%) | 1 | 0/17 (0%) | 0 |
| Nervous system disorders | ||||||
| Amnesia | 1/16 (6.3%) | 1 | 0/16 (0%) | 0 | 0/17 (0%) | 0 |
| Syncope | 0/16 (0%) | 0 | 0/16 (0%) | 0 | 1/17 (5.9%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 0/16 (0%) | 0 | 1/16 (6.3%) | 1 | 0/17 (0%) | 0 |
| Snoring | 0/16 (0%) | 0 | 1/16 (6.3%) | 1 | 0/17 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Eczema | 0/16 (0%) | 0 | 1/16 (6.3%) | 1 | 0/17 (0%) | 0 |
| Rash | 0/16 (0%) | 0 | 1/16 (6.3%) | 1 | 0/17 (0%) | 0 |
| Rash Maculo-Papular | 0/16 (0%) | 0 | 0/16 (0%) | 0 | 1/17 (5.9%) | 1 |
| Vascular disorders | ||||||
| Haematoma | 0/16 (0%) | 0 | 1/16 (6.3%) | 1 | 0/17 (0%) | 0 |
| Hot flush | 0/16 (0%) | 0 | 1/16 (6.3%) | 1 | 0/17 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Novo Nordisk reserves the right to not release data until specified milestones (e.g. when clinical trial report is available), including right to not release interim results because such action can invalidate results of the entire trial. At trial end, one or more manuscripts for publication will be prepared collaboratively between Investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for less than 60 days to protect intellectual property.
Results Point of Contact
| Name/Title | Public Access to Clinical Trials |
|---|---|
| Organization | Novo Nordisk A/S |
| Phone | |
| clinicaltrials@novonordisk.com |
Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00620282
Other Study ID Numbers:
- NN2211-1799
First Posted:
Feb 21, 2008
Last Update Posted:
Mar 8, 2017
Last Verified:
Jan 1, 2017