Diabetes, Diabetes Mellitus, Type 2
Conditions
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.
Interventions
DRUGliraglutide
Stepwise dose increase, s.c. (under the skin) injection, once daily
DRUGplacebo
Liraglutide placebo, stepwise dose increase, s.c. (under the skin) injection, once daily
DRUGglimepiride
Tablets, 1 - 4 mg daily
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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. |
| Fasting Lipid Profile - Change in HDL-C | week 0, week 12 | Change in HDL-C |
Countries
United States
Participant flow
Recruitment details
The trial was conducted at one site in the United States of America (USA).
Participants by arm
| Arm | Count |
|---|---|
| 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) | 16 |
| 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) | 16 |
| Glimepiride Glimepiride 4 mg administered orally, once-daily, open-label, weeks 0-12 | 17 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Arterial line unable to be placed | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Lira 1.8 | Placebo | Glimepiride | Total |
|---|---|---|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 9 | 60.3 years STANDARD_DEVIATION 7.3 | 57.7 years STANDARD_DEVIATION 5.3 | 58.5 years STANDARD_DEVIATION 7.3 |
| Body Mass Index (BMI) | 32.7 kg/m^2 STANDARD_DEVIATION 4.5 | 31.6 kg/m^2 STANDARD_DEVIATION 4.2 | 31.1 kg/m^2 STANDARD_DEVIATION 4.9 | 31.8 kg/m^2 STANDARD_DEVIATION 4.5 |
| Body Weight | 95.09 kg STANDARD_DEVIATION 13.12 | 90.63 kg STANDARD_DEVIATION 13.47 | 91.99 kg STANDARD_DEVIATION 13.97 | 92.56 kg STANDARD_DEVIATION 13.38 |
| Duration of Diabetes | 5.3 years STANDARD_DEVIATION 4.1 | 8.4 years STANDARD_DEVIATION 4.6 | 6.8 years STANDARD_DEVIATION 8.1 | 6.8 years STANDARD_DEVIATION 6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 16 Participants | 17 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fasting Plasma Glucose (FPG) | 160.8 mg/dL STANDARD_DEVIATION 31.2 | 145.2 mg/dL STANDARD_DEVIATION 20.1 | 163.3 mg/dL STANDARD_DEVIATION 33.3 | 156.6 mg/dL STANDARD_DEVIATION 29.4 |
| Glycosylated Haemoglobin A1c (HbA1c) | 7.2 percentage of total haemoglobin STANDARD_DEVIATION 0.5 | 7.0 percentage of total haemoglobin STANDARD_DEVIATION 0.5 | 7.3 percentage of total haemoglobin STANDARD_DEVIATION 0.5 | 7.2 percentage of total haemoglobin STANDARD_DEVIATION 0.5 |
| High density lipoprotein (HDL-C) | 39.6 mg/dL STANDARD_DEVIATION 10 | 39.2 mg/dL STANDARD_DEVIATION 7.5 | 43.5 mg/dL STANDARD_DEVIATION 10.3 | 40.8 mg/dL STANDARD_DEVIATION 9.4 |
| Low density lipoprotein (LDL-C) | 102.8 mg/dL STANDARD_DEVIATION 31.3 | 92.5 mg/dL STANDARD_DEVIATION 23.5 | 94.1 mg/dL STANDARD_DEVIATION 18.4 | 96.4 mg/dL STANDARD_DEVIATION 24.8 |
| Previous Anti-diabetic Treatment Diet/Exercise | 2 participants | 1 participants | 2 participants | 5 participants |
| Previous Anti-diabetic Treatment Metformin | 14 participants | 15 participants | 15 participants | 44 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 16 Participants | 17 Participants | 49 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 11 Participants | 31 Participants |
| Total Cholesterol (TC) | 170.2 mg/dL STANDARD_DEVIATION 34.4 | 157.5 mg/dL STANDARD_DEVIATION 32 | 160.2 mg/dL STANDARD_DEVIATION 24.1 | 162.6 mg/dL STANDARD_DEVIATION 30.2 |
| Triglycerides (TG) | 165.8 mg/dL STANDARD_DEVIATION 72.9 | 145.9 mg/dL STANDARD_DEVIATION 57.5 | 141.4 mg/dL STANDARD_DEVIATION 67.4 | 150.8 mg/dL STANDARD_DEVIATION 65.7 |
| Tumor necrosis factor-alpha (TNF-alpha) | 2.1 pg/mL STANDARD_DEVIATION 1.5 | 1.4 pg/mL STANDARD_DEVIATION 0.8 | 1.4 pg/mL STANDARD_DEVIATION 0.5 | 1.6 pg/mL STANDARD_DEVIATION 1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 16 | 9 / 16 | 5 / 17 |
| serious Total, serious adverse events | 0 / 16 | 1 / 16 | 0 / 17 |
Outcome results
Primary
Change in Acetylcholine (ACh)-Mediated Forearm Blood Flow (FBF)
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
Population: The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Acetylcholine (ACh)-Mediated Forearm Blood Flow (FBF) | 4.244 mL/100 mL/min | Standard Error 2.551 |
| Placebo | Change in Acetylcholine (ACh)-Mediated Forearm Blood Flow (FBF) | -3.187 mL/100 mL/min | Standard Error 2.758 |
| Glimepiride | Change in Acetylcholine (ACh)-Mediated Forearm Blood Flow (FBF) | 2.164 mL/100 mL/min | Standard Error 2.568 |
Comparison: 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.p-value: 0.054995% CI: [-0.164, 15.025]ANCOVA
Comparison: 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.p-value: 0.568195% CI: [-5.215, 9.375]ANCOVA
Comparison: 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.p-value: 0.166895% CI: [-2.323, 13.024]ANCOVA
Secondary
Biomarkers of Cardiovascular Risk - Change in TNF-alpha
Change in TNF-alpha
Time frame: week 0, week 12
Population: The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Biomarkers of Cardiovascular Risk - Change in TNF-alpha | -0.024 pg/mL | Standard Error 0.232 |
| Placebo | Biomarkers of Cardiovascular Risk - Change in TNF-alpha | 0.397 pg/mL | Standard Error 0.25 |
| Glimepiride | Biomarkers of Cardiovascular Risk - Change in TNF-alpha | -0.0050 pg/mL | Standard Error 0.231 |
Comparison: 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.p-value: 0.228295% CI: [-1.118, 0.278]ANCOVA
Comparison: 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.p-value: 0.956995% CI: [-0.697, 0.661]ANCOVA
Comparison: 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.p-value: 0.246595% CI: [-1.097, 0.293]ANCOVA
Secondary
Change in Body Weight
Time frame: week 0, week 12
Population: The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Body Weight | -1.821 kg | Standard Error 0.455 |
| Placebo | Change in Body Weight | -0.293 kg | Standard Error 0.486 |
| Glimepiride | Change in Body Weight | 1.038 kg | Standard Error 0.441 |
Comparison: 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.p-value: 0.026895% CI: [-2.873, -0.184]ANCOVA
Comparison: 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.95% CI: [-4.139, -1.579]ANCOVA
Comparison: 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.p-value: 0.048695% CI: [0.009, 2.653]ANCOVA
Secondary
Change in Fasting Plasma Glucose (FPG)
Change in FPG
Time frame: week 0, week 12
Population: The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Fasting Plasma Glucose (FPG) | -41.672 mg/dL | Standard Error 3.643 |
| Placebo | Change in Fasting Plasma Glucose (FPG) | -6.067 mg/dL | Standard Error 4.079 |
| Glimepiride | Change in Fasting Plasma Glucose (FPG) | -32.019 mg/dL | Standard Error 3.708 |
Comparison: 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.95% CI: [-46.797, -24.413]ANCOVA
Comparison: 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.p-value: 0.067795% CI: [-20.041, 0.736]ANCOVA
Comparison: 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.95% CI: [-37.429, -14.475]ANCOVA
Secondary
Change in HbA1c (Glycosylated Haemoglobin A1c)
Percentage point change in HbA1c
Time frame: week 0, week 12
Population: The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in HbA1c (Glycosylated Haemoglobin A1c) | -0.629 percentage of total haemoglobin | Standard Error 0.109 |
| Placebo | Change in HbA1c (Glycosylated Haemoglobin A1c) | -0.094 percentage of total haemoglobin | Standard Error 0.121 |
| Glimepiride | Change in HbA1c (Glycosylated Haemoglobin A1c) | -0.552 percentage of total haemoglobin | Standard Error 0.112 |
Comparison: 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.p-value: 0.002395% CI: [-0.868, -0.203]ANCOVA
Comparison: 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.p-value: 0.620795% CI: [-0.391, 0.236]ANCOVA
Comparison: 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.p-value: 0.009895% CI: [-0.8, -0.116]ANCOVA
Secondary
Change in Mean Postprandial Glucose (PPG) Based on Self-measured 7-point Plasma Glucose Profiles
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
Population: The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Mean Postprandial Glucose (PPG) Based on Self-measured 7-point Plasma Glucose Profiles | -32.175 mg/dL | Standard Error 9.104 |
| Placebo | Change in Mean Postprandial Glucose (PPG) Based on Self-measured 7-point Plasma Glucose Profiles | -20.304 mg/dL | Standard Error 10.619 |
| Glimepiride | Change in Mean Postprandial Glucose (PPG) Based on Self-measured 7-point Plasma Glucose Profiles | -35.99 mg/dL | Standard Error 8.673 |
Comparison: 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.p-value: 0.412195% CI: [-40.943, 17.201]ANCOVA
Comparison: 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.p-value: 0.762295% CI: [-21.618, 29.247]ANCOVA
Comparison: 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.p-value: 0.265195% CI: [-43.838, 12.466]ANCOVA
Secondary
Change in Sodium Nitroprusside (SNP)-Mediated Forearm Blood Flow (FBF)
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
Population: The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Sodium Nitroprusside (SNP)-Mediated Forearm Blood Flow (FBF) | 3.455 mL/100 mL/min | Standard Error 2.681 |
| Placebo | Change in Sodium Nitroprusside (SNP)-Mediated Forearm Blood Flow (FBF) | -1.044 mL/100 mL/min | Standard Error 2.893 |
| Glimepiride | Change in Sodium Nitroprusside (SNP)-Mediated Forearm Blood Flow (FBF) | 2.746 mL/100 mL/min | Standard Error 2.67 |
Comparison: 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.p-value: 0.264895% CI: [-3.535, 12.534]ANCOVA
Comparison: 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.p-value: 0.851895% CI: [-6.904, 8.322]ANCOVA
Comparison: 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.p-value: 0.343595% CI: [-4.194, 11.774]ANCOVA
Secondary
Fasting Lipid Profile - Change in HDL-C
Change in HDL-C
Time frame: week 0, week 12
Population: The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Fasting Lipid Profile - Change in HDL-C | 0.393 mg/dL | Standard Error 1.053 |
| Placebo | Fasting Lipid Profile - Change in HDL-C | 0.562 mg/dL | Standard Error 1.133 |
| Glimepiride | Fasting Lipid Profile - Change in HDL-C | 1.116 mg/dL | Standard Error 1.074 |
Comparison: 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.p-value: 0.913195% CI: [-3.273, 2.935]ANCOVA
Comparison: 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.p-value: 0.636295% CI: [-3.785, 2.339]ANCOVA
Comparison: 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.p-value: 0.728395% CI: [-2.643, 3.751]ANCOVA
Secondary
Fasting Lipid Profile - Change in LDL-C
Change in LDL-C
Time frame: week 0, week 12
Population: The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Fasting Lipid Profile - Change in LDL-C | 1.243 mg/dL | Standard Error 4.294 |
| Placebo | Fasting Lipid Profile - Change in LDL-C | -2.459 mg/dL | Standard Error 4.551 |
| Glimepiride | Fasting Lipid Profile - Change in LDL-C | -1.529 mg/dL | Standard Error 4.275 |
Comparison: 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.p-value: 0.558395% CI: [-8.96, 16.365]ANCOVA
Comparison: 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.p-value: 0.651795% CI: [-9.537, 15.082]ANCOVA
Comparison: 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.p-value: 0.882295% CI: [-11.646, 13.505]ANCOVA
Secondary
Fasting Lipid Profile - Change in Total Cholesterol (TC)
Change in TC
Time frame: week 0, week 12
Population: The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Fasting Lipid Profile - Change in Total Cholesterol (TC) | 2.006 mg/dL | Standard Error 5.274 |
| Placebo | Fasting Lipid Profile - Change in Total Cholesterol (TC) | 4.243 mg/dL | Standard Error 5.597 |
| Glimepiride | Fasting Lipid Profile - Change in Total Cholesterol (TC) | 0.094 mg/dL | Standard Error 5.239 |
Comparison: 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.p-value: 0.773695% CI: [-17.829, 13.354]ANCOVA
Comparison: 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.p-value: 0.799395% CI: [-13.168, 16.991]ANCOVA
Comparison: 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.p-value: 0.590395% CI: [-19.582, 11.284]ANCOVA
Secondary
Fasting Lipid Profile - Change in Triglycerides (TG)
Change in TG
Time frame: week 0, week 12
Population: The ANCOVA full analysis set (FAS) includes all randomised subjects for whom data points could be collected at end of trial.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Fasting Lipid Profile - Change in Triglycerides (TG) | -8.163 mg/dL | Standard Error 13.471 |
| Placebo | Fasting Lipid Profile - Change in Triglycerides (TG) | 28.546 mg/dL | Standard Error 14.282 |
| Glimepiride | Fasting Lipid Profile - Change in Triglycerides (TG) | -4.377 mg/dL | Standard Error 13.399 |
Comparison: 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.p-value: 0.069495% CI: [-76.467, 3.048]ANCOVA
Comparison: 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.p-value: 0.84495% CI: [-42.373, 34.801]ANCOVA
Comparison: 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.p-value: 0.099495% CI: [-72.353, 6.507]ANCOVA
Secondary
Haematology and Biochemistry Tests - Number of Subjects With Blood Urea Nitrogen (BUN) Values Outside Reference Range
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lira 1.8 | Haematology and Biochemistry Tests - Number of Subjects With Blood Urea Nitrogen (BUN) Values Outside Reference Range | Week 0 | 1 participants |
| Lira 1.8 | Haematology and Biochemistry Tests - Number of Subjects With Blood Urea Nitrogen (BUN) Values Outside Reference Range | Week 12 | 1 participants |
| Placebo | Haematology and Biochemistry Tests - Number of Subjects With Blood Urea Nitrogen (BUN) Values Outside Reference Range | Week 0 | 0 participants |
| Placebo | Haematology and Biochemistry Tests - Number of Subjects With Blood Urea Nitrogen (BUN) Values Outside Reference Range | Week 12 | 2 participants |
| Glimepiride | Haematology and Biochemistry Tests - Number of Subjects With Blood Urea Nitrogen (BUN) Values Outside Reference Range | Week 0 | 1 participants |
| Glimepiride | Haematology and Biochemistry Tests - Number of Subjects With Blood Urea Nitrogen (BUN) Values Outside Reference Range | Week 12 | 0 participants |
Secondary
Haematology and Biochemistry Tests - Number of Subjects With Creatinine Values Outside Reference Range
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lira 1.8 | Haematology and Biochemistry Tests - Number of Subjects With Creatinine Values Outside Reference Range | Week 0 | 1 participants |
| Lira 1.8 | Haematology and Biochemistry Tests - Number of Subjects With Creatinine Values Outside Reference Range | Week 12 | 1 participants |
| Placebo | Haematology and Biochemistry Tests - Number of Subjects With Creatinine Values Outside Reference Range | Week 0 | 3 participants |
| Placebo | Haematology and Biochemistry Tests - Number of Subjects With Creatinine Values Outside Reference Range | Week 12 | 2 participants |
| Glimepiride | Haematology and Biochemistry Tests - Number of Subjects With Creatinine Values Outside Reference Range | Week 0 | 5 participants |
| Glimepiride | Haematology and Biochemistry Tests - Number of Subjects With Creatinine Values Outside Reference Range | Week 12 | 2 participants |
Secondary
Number of Hypoglycaemic Episodes
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lira 1.8 | Number of Hypoglycaemic Episodes | Minor | 1 episodes |
| Lira 1.8 | Number of Hypoglycaemic Episodes | Major | 0 episodes |
| Lira 1.8 | Number of Hypoglycaemic Episodes | Symptoms Only | 3 episodes |
| Placebo | Number of Hypoglycaemic Episodes | Minor | 0 episodes |
| Placebo | Number of Hypoglycaemic Episodes | Major | 0 episodes |
| Placebo | Number of Hypoglycaemic Episodes | Symptoms Only | 0 episodes |
| Glimepiride | Number of Hypoglycaemic Episodes | Major | 0 episodes |
| Glimepiride | Number of Hypoglycaemic Episodes | Symptoms Only | 4 episodes |
| Glimepiride | Number of Hypoglycaemic Episodes | Minor | 10 episodes |