Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in North America (the United States of America (USA) and Mexico). The trial is designed to evaluate the effects of treatment with liraglutide versus glimepiride in subjects with type 2 diabetes. The trial is a 52-week randomised, double-blind trial period plus a 52-week open-label extension (week 104) followed by an additional 156-week continued open-label extension. The total duration of the treatment period is planned to be 260 weeks (5 years).
Interventions
DRUGliraglutide
1.8 mg for s.c. (under the skin) injection
DRUGglimepiride
8 mg capsule
DRUGplacebo
Glimepiride placebo, 8mg capsule
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes * TTreatment with diet/exercise or with not more than half maximal dose of oral anti-diabetic drugs alone for at least 2 months * Diet/exercise treated subjects with HbA1c between 7.0% and 11%, inclusive * OAD (oral anti-diabetic drug) treated subjects with HbA1c between 7.0% and 10%, inclusive * Body Mass Index (BMI) less than or equal to 45 kg/m\^2
Exclusion criteria
* Treatment with insulin for the last 3 months, except short-term treatment for intercurrent illness * Treatment with any drug that could interfere with the glucose level (besides use of a single anti-diabetic compound) * Any serious medical condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 | week 0, week 52 | Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 52 weeks (end of double-blind period) |
| Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 104 | week 0, week 104 | Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 104 weeks (end of 52-week extension) |
| Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 156 | week 0, week 156 | Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 156 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Plasma Glucose at Week 52 | week 0, week 52 | Change in fasting plasma glucose (FPG) from baseline (week 0) to 52 weeks (end of double-blind period) |
| Change in Fasting Plasma Glucose at Week 104 | week 0, week 104 | Change in fasting plasma glucose (FPG) from baseline (week 0) to 104 weeks (end of 52-week extension) |
| Change in Fasting Plasma Glucose at Week 156 | week 0, week 156 | Change in fasting plasma glucose (FPG) from baseline (week 0) to 156 weeks |
| Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52 | week 0, week 52 | Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 52 weeks (end of double-blind period). The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. |
| Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104 | week 0, week 104 | Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 104 weeks (end of 52-week extension). The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. |
| Change in Body Weight at Week 52 | week 0, week 52 | Change in body weight from baseline (week 0) to 52 weeks (end of double-blind period) |
| Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52 | week 0, week 52 | Change in mean prandial increments of plasma glucose from baseline (week 0) to 52 weeks (end of double-blind period). The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three. |
| Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104 | week 0, week 104 | Change in mean prandial increments of plasma glucose from baseline (week 0) to 104 weeks (end of 52-week extension). The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three. |
| Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156 | week 0, week 156 | Change in mean prandial increments (incr.) of plasma glucose from baseline (week 0) to 156 weeks. The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three. |
| Hypoglycaemic Episodes | weeks 0-104 | Total number of hypoglycaemic episodes occuring from baseline (week 0) to 104 weeks (end of the 52-week extension). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. 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 Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156 | week 0, week 156 | Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 156 weeks. The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. |
| Change in Body Weight at Week 104 | week 0, week 104 | Change in body weight from baseline (week 0) to 104 weeks (end of 52-week extension) |
| Change in Body Weight at Week 156 | week 0, week 156 | Change in body weight from baseline (week 0) to 156 weeks |
Countries
Mexico, Puerto Rico, United States
Participant flow
Recruitment details
A total of 138 centres in two countries: United States of America (USA) (126) and Mexico (12).
Pre-assignment details
Subjects with type 2 diabetes treated with diet/exercise or OAD (Oral Anti-Diabetic Drug) monotherapy for at least 2 months were eligible. One subject randomised to the liraglutide 1.8 mg group was withdrawn from the study prior to dosing due to protocol non compliance, subject was not included in the intent-to-treat (ITT) or safety analysis sets.
Participants by arm
| Arm | Count |
|---|---|
| Lira 1.8 Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195) | 247 |
| Lira 1.2 Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195) | 251 |
| Glimepiride Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195) | 248 |
| Total | 746 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Additional Open-Label Extension 91 Weeks | Adverse Event | 1 | 1 | 0 |
| Additional Open-Label Extension 91 Weeks | Lack of Efficacy | 24 | 14 | 16 |
| Additional Open-Label Extension 91 Weeks | Not specified in study report | 2 | 5 | 3 |
| Additional Open-Label Extension 91 Weeks | Protocol Violation | 1 | 1 | 1 |
| Double-Blind Period 52 Weeks | Adverse Event | 18 | 25 | 15 |
| Double-Blind Period 52 Weeks | Lack of Efficacy | 9 | 15 | 25 |
| Double-Blind Period 52 Weeks | Not specified in study report | 36 | 38 | 51 |
| Double-Blind Period 52 Weeks | Protocol Violation | 11 | 11 | 5 |
| Open-Label Extension 52 Weeks | Adverse Event | 5 | 5 | 2 |
| Open-Label Extension 52 Weeks | Lack of Efficacy | 12 | 15 | 21 |
| Open-Label Extension 52 Weeks | Not specified in study report | 19 | 16 | 14 |
| Open-Label Extension 52 Weeks | Protocol Violation | 4 | 3 | 3 |
Baseline characteristics
| Characteristic | Lira 1.8 | Total | Glimepiride | Lira 1.2 |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 25 Participants | 108 Participants | 40 Participants | 43 Participants |
| Age, Categorical Between 18 and 65 years | 222 Participants | 638 Participants | 208 Participants | 208 Participants |
| Age, Continuous | 52.0 years STANDARD_DEVIATION 10.8 | 53.0 years STANDARD_DEVIATION 10.9 | 53.4 years STANDARD_DEVIATION 10.9 | 53.7 years STANDARD_DEVIATION 11 |
| Body Mass Index (BMI) | 32.8 kg/m^2 STANDARD_DEVIATION 6.3 | 33.1 kg/m^2 STANDARD_DEVIATION 5.8 | 33.2 kg/m^2 STANDARD_DEVIATION 5.6 | 33.2 kg/m^2 STANDARD_DEVIATION 5.6 |
| Duration of diabetes | 5.3 years STANDARD_DEVIATION 5.1 | 5.4 years STANDARD_DEVIATION 5.3 | 5.6 years STANDARD_DEVIATION 5.1 | 5.2 years STANDARD_DEVIATION 5.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 87 Participants | 261 Participants | 93 Participants | 81 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 160 Participants | 485 Participants | 155 Participants | 170 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| HbA1c (Glycosylated Haemoglobin A1c) | 8.3 percentage of total haemoglobin STANDARD_DEVIATION 1.1 | 8.3 percentage of total haemoglobin STANDARD_DEVIATION 1.1 | 8.4 percentage of total haemoglobin STANDARD_DEVIATION 1.2 | 8.3 percentage of total haemoglobin STANDARD_DEVIATION 1 |
| Previous anti-diabetic treatment Diet/Exercise | 87 participants | 272 participants | 94 participants | 91 participants |
| Previous anti-diabetic treatment Monotherapy | 160 participants | 474 participants | 154 participants | 160 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 26 Participants | 9 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 30 Participants | 94 Participants | 30 Participants | 34 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 | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 17 Participants | 46 Participants | 17 Participants | 12 Participants |
| Race (NIH/OMB) White | 186 Participants | 578 Participants | 192 Participants | 200 Participants |
| Region of Enrollment Mexico | 52 participants | 171 participants | 66 participants | 53 participants |
| Region of Enrollment United States | 195 participants | 575 participants | 182 participants | 198 participants |
| Sex: Female, Male Female | 126 Participants | 375 Participants | 115 Participants | 134 Participants |
| Sex: Female, Male Male | 121 Participants | 371 Participants | 133 Participants | 117 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 183 / 246 | 181 / 251 | 148 / 248 | 40 / 62 | 37 / 53 | 13 / 28 |
| serious Total, serious adverse events | 22 / 246 | 23 / 251 | 20 / 248 | 5 / 62 | 1 / 53 | 2 / 28 |
Outcome results
Primary
Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 104
Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 104 weeks (end of 52-week extension)
Time frame: week 0, week 104
Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 104 | -0.88 percentage point of total HbA1c | Standard Error 0.09 |
| Lira 1.2 | Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 104 | -0.59 percentage point of total HbA1c | Standard Error 0.09 |
| Glimepiride | Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 104 | -0.28 percentage point of total HbA1c | Standard Error 0.09 |
Comparison: Change in glycosylated haemoglobin (HbA1c) from baseline to end of treatment at 104 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous oral antidiabetic drug (OAD) treatment as fixed effects and baseline HbA1c as covariate.p-value: <0.000195% CI: [-0.83, -0.38]ANCOVA
Comparison: Change in glycosylated haemoglobin (HbA1c) from baseline to end of treatment at 104 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous oral antidiabetic drug (OAD) treatment as fixed effects and baseline HbA1c as covariate.p-value: 0.007695% CI: [-0.54, -0.08]ANCOVA
Comparison: Change in glycosylated haemoglobin (HbA1c) from baseline to end of treatment at 104 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous oral antidiabetic drug (OAD) treatment as fixed effects and baseline HbA1c as covariate.p-value: 0.012995% CI: [-0.52, -0.06]ANCOVA
Primary
Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 156
Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 156 weeks
Time frame: week 0, week 156
Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 156 | -0.71 percentage point of total HbA1c | Standard Error 0.09 |
| Lira 1.2 | Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 156 | -0.44 percentage point of total HbA1c | Standard Error 0.09 |
| Glimepiride | Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 156 | -0.16 percentage point of total HbA1c | Standard Error 0.08 |
Comparison: Change in glycosylated haemoglobin (HbA1c) from baseline to end of treatment at 156 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country, and previous oral antidiabetic drug (OAD) treatment as fixed effects and baseline HbA1c as covariate.p-value: <0.000195% CI: [-0.77, -0.34]ANCOVA
Comparison: Change in glycosylated haemoglobin (HbA1c) from baseline to end of treatment at 156 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country, and previous oral antidiabetic drug (OAD) treatment as fixed effects and baseline HbA1c as covariate.p-value: 0.012295% CI: [-0.49, -0.06]ANCOVA
Comparison: Change in glycosylated haemoglobin (HbA1c) from baseline to end of treatment at 156 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country, and previous oral antidiabetic drug (OAD) treatment as fixed effects and baseline HbA1c as covariate.p-value: 0.012395% CI: [-0.49, -0.06]ANCOVA
Primary
Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52
Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 52 weeks (end of double-blind period)
Time frame: week 0, week 52
Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 | -1.14 percentage point of total HbA1c | Standard Error 0.08 |
| Lira 1.2 | Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 | -0.84 percentage point of total HbA1c | Standard Error 0.08 |
| Glimepiride | Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 | -0.51 percentage point of total HbA1c | Standard Error 0.08 |
Comparison: Change in glycosylated haemoglobin (HbA1c) from baseline to end of treatment at 52 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous oral antidiabetic drug (OAD) treatment as fixed effects and baseline HbA1c as covariate.p-value: <0.000195% CI: [-0.83, -0.42]ANCOVA
Comparison: Change in glycosylated haemoglobin (HbA1c) from baseline to end of treatment at 52 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous oral antidiabetic drug (OAD) treatment as fixed effects and baseline HbA1c as covariate.p-value: 0.001495% CI: [-0.53, -0.13]ANCOVA
Comparison: Change in glycosylated haemoglobin (HbA1c) from baseline to end of treatment at 52 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous oral antidiabetic drug (OAD) treatment as fixed effects and baseline HbA1c as covariate.p-value: 0.004695% CI: [-0.5, -0.09]ANCOVA
Secondary
Change in Body Weight at Week 104
Change in body weight from baseline (week 0) to 104 weeks (end of 52-week extension)
Time frame: week 0, week 104
Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Body Weight at Week 104 | -2.70 kg | Standard Error 0.32 |
| Lira 1.2 | Change in Body Weight at Week 104 | -1.89 kg | Standard Error 0.31 |
| Glimepiride | Change in Body Weight at Week 104 | 0.95 kg | Standard Error 0.3 |
Comparison: Change in body weight from baseline to end of treatment at 104 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline body weight as covariate.p-value: <0.000195% CI: [-4.44, -2.86]ANCOVA
Comparison: Change in body weight from baseline to end of treatment at 104 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline body weight as covariate.p-value: <0.000195% CI: [-3.63, -2.06]ANCOVA
Comparison: Change in body weight from baseline to end of treatment at 104 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline body weight as covariate.p-value: 0.046295% CI: [-1.59, -0.01]ANCOVA
Secondary
Change in Body Weight at Week 156
Change in body weight from baseline (week 0) to 156 weeks
Time frame: week 0, week 156
Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Body Weight at Week 156 | -2.43 kg | Standard Error 0.32 |
| Lira 1.2 | Change in Body Weight at Week 156 | -1.68 kg | Standard Error 0.32 |
| Glimepiride | Change in Body Weight at Week 156 | 1.05 kg | Standard Error 0.31 |
Comparison: Change in body weight from baseline to end of treatment at 156 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country, and previous anti-diabetic treatment as fixed effects and baseline body weight as covariate.p-value: <0.000195% CI: [-4.28, -2.68]ANCOVA
Comparison: Change in body weight from baseline to end of treatment at 156 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country, and previous anti-diabetic treatment as fixed effects and baseline body weight as covariate.p-value: <0.000195% CI: [-3.52, -1.93]ANCOVA
Comparison: Change in body weight from baseline to end of treatment at 156 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country, and previous anti-diabetic treatment as fixed effects and baseline body weight as covariance.p-value: 0.064295% CI: [-1.55, 0.05]ANCOVA
Secondary
Change in Body Weight at Week 52
Change in body weight from baseline (week 0) to 52 weeks (end of double-blind period)
Time frame: week 0, week 52
Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Body Weight at Week 52 | -2.45 kg | Standard Error 0.28 |
| Lira 1.2 | Change in Body Weight at Week 52 | -2.05 kg | Standard Error 0.28 |
| Glimepiride | Change in Body Weight at Week 52 | 1.12 kg | Standard Error 0.27 |
Comparison: Change in body weight from baseline to end of treatment at 52 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline body weight as covariate.p-value: <0.000195% CI: [-4.28, -2.87]ANCOVA
Comparison: Change in body weight from baseline to end of treatment at 52 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline body weight as covariate.p-value: <0.000195% CI: [-3.87, -2.47]ANCOVA
Comparison: Change in body weight from baseline to end of treatment at 52 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline body weight as covariate.p-value: 0.258495% CI: [-1.11, 0.3]ANCOVA
Secondary
Change in Fasting Plasma Glucose at Week 104
Change in fasting plasma glucose (FPG) from baseline (week 0) to 104 weeks (end of 52-week extension)
Time frame: week 0, week 104
Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Fasting Plasma Glucose at Week 104 | -15.82 mg/dL | Standard Error 3.85 |
| Lira 1.2 | Change in Fasting Plasma Glucose at Week 104 | -9.36 mg/dL | Standard Error 3.85 |
| Glimepiride | Change in Fasting Plasma Glucose at Week 104 | 1.97 mg/dL | Standard Error 3.66 |
Comparison: Change in fasting plasma glucose (FPG) from baseline to end of treatment at 104 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline FPG as covariate.p-value: 0.000395% CI: [-27.48, -8.09]ANCOVA
Comparison: Change in fasting plasma glucose (FPG) from baseline to end of treatment at 104 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline FPG as covariate.p-value: 0.021795% CI: [-20.99, -1.66]ANCOVA
Comparison: Change in fasting plasma glucose (FPG) from baseline to end of treatment at 104 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline FPG as covariate.p-value: 0.194295% CI: [-16.23, 3.3]ANCOVA
Secondary
Change in Fasting Plasma Glucose at Week 156
Change in fasting plasma glucose (FPG) from baseline (week 0) to 156 weeks
Time frame: week 0, week 156
Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Fasting Plasma Glucose at Week 156 | -12.06 mg/dL | Standard Error 3.8 |
| Lira 1.2 | Change in Fasting Plasma Glucose at Week 156 | -5.45 mg/dL | Standard Error 3.8 |
| Glimepiride | Change in Fasting Plasma Glucose at Week 156 | 4.57 mg/dL | Standard Error 3.62 |
Comparison: Change in fasting plasma glucose (FPG) from baseline to end of treatment at 156 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline FPG as covariate.p-value: 0.000795% CI: [-26.19, -7.06]ANCOVA
Comparison: Change in fasting plasma glucose (FPG) from baseline to end of treatment at 156 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline FPG as covariate.p-value: 0.039595% CI: [-19.56, -0.49]ANCOVA
Comparison: Change in fasting plasma glucose (FPG) from baseline to end of treatment at 156 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline FPG as covariate.p-value: 0.178995% CI: [-16.24, 3.03]ANCOVA
Secondary
Change in Fasting Plasma Glucose at Week 52
Change in fasting plasma glucose (FPG) from baseline (week 0) to 52 weeks (end of double-blind period)
Time frame: week 0, week 52
Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Fasting Plasma Glucose at Week 52 | -25.57 mg/dL | Standard Error 3.5 |
| Lira 1.2 | Change in Fasting Plasma Glucose at Week 52 | -15.21 mg/dL | Standard Error 3.5 |
| Glimepiride | Change in Fasting Plasma Glucose at Week 52 | -5.29 mg/dL | Standard Error 3.33 |
Comparison: Change in fasting plasma glucose (FPG) from baseline to end of treatment at 52 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline FPG as covariate.p-value: <0.000195% CI: [-29.09, -11.46]ANCOVA
Comparison: Change in fasting plasma glucose (FPG) from baseline to end of treatment at 52 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline FPG as covariate.p-value: 0.02795% CI: [-18.7, -1.12]ANCOVA
Comparison: Change in fasting plasma glucose (FPG) from baseline to end of treatment at 52 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline FPG as covariate.p-value: 0.022395% CI: [-19.24, -1.48]ANCOVA
Secondary
Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104
Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 104 weeks (end of 52-week extension). The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min.
Time frame: week 0, week 104
Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104 | -37.15 mg/dL | Standard Error 3.64 |
| Lira 1.2 | Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104 | -27.34 mg/dL | Standard Error 3.68 |
| Glimepiride | Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104 | -24.85 mg/dL | Standard Error 3.58 |
Comparison: Change in postprandial glucose (PPG) from baseline to end of treatment at 104 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline PPG as covariate.p-value: 0.010595% CI: [-21.71, -2.89]ANCOVA
Comparison: Change in postprandial glucose (PPG) from baseline to end of treatment at 104 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline PPG as covariate.p-value: 0.60695% CI: [-11.95, 6.98]ANCOVA
Comparison: Change in postprandial glucose (PPG) from baseline to end of treatment at 104 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline PPG as covariate.p-value: 0.039295% CI: [-19.14, -0.49]ANCOVA
Secondary
Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156
Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 156 weeks. The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min.
Time frame: week 0, week 156
Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156 | -34.83 mg/dL | Standard Error 3.65 |
| Lira 1.2 | Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156 | -25.68 mg/dL | Standard Error 3.69 |
| Glimepiride | Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156 | -23.84 mg/dL | Standard Error 3.59 |
Comparison: Change in postprandial glucose (PPG) from baseline to end of treatment at 156 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline PPG as covariate.p-value: 0.022795% CI: [-20.42, -1.54]ANCOVA
Comparison: Change in postprandial glucose (PPG) from baseline to end of treatment at 156 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline PPG as covariate.p-value: 0.704795% CI: [-11.33, 7.66]ANCOVA
Comparison: Change in postprandial glucose (PPG) from baseline to end of treatment at 156 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline PPG as covariate.p-value: 0.055395% CI: [-18.51, 0.21]ANCOVA
Secondary
Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52
Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 52 weeks (end of double-blind period). The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min.
Time frame: week 0, week 52
Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52 | -37.4 mg/dL | Standard Error 3.37 |
| Lira 1.2 | Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52 | -30.8 mg/dL | Standard Error 3.4 |
| Glimepiride | Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52 | -24.5 mg/dL | Standard Error 3.32 |
Comparison: Change in mean postprandial glucose (PPG) from baseline to end of treatment at 52 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline PPG as covariate.p-value: 0.003895% CI: [-21.6, -4.2]ANCOVA
Comparison: Change in postprandial glucose (PPG) from baseline to end of treatment at 52 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline PPG as covariate.p-value: 0.161695% CI: [-15, 2.5]ANCOVA
Comparison: Change in postprandial glucose (PPG) from baseline to end of treatment at 52 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline PPG as covariate.p-value: 0.131995% CI: [-15.3, 2]ANCOVA
Secondary
Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104
Change in mean prandial increments of plasma glucose from baseline (week 0) to 104 weeks (end of 52-week extension). The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three.
Time frame: week 0, week 104
Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104 | -11.76 mg/dL | Standard Error 2.11 |
| Lira 1.2 | Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104 | -8.28 mg/dL | Standard Error 2.14 |
| Glimepiride | Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104 | -7.95 mg/dL | Standard Error 2.08 |
Comparison: Change in prandial increments of plasma glucose from baseline to end of treatment at 104 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline value as covariate.p-value: 0.17295% CI: [-9.28, 1.66]ANCOVA
Comparison: Change in prandial increments of plasma glucose from baseline to end of treatment at 104 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline value as covariate.p-value: 0.90695% CI: [-5.82, 5.16]ANCOVA
Comparison: Change in prandial increments of plasma glucose from baseline to end of treatment at 104 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline value as covariate.p-value: 0.208995% CI: [-8.91, 1.95]ANCOVA
Secondary
Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156
Change in mean prandial increments (incr.) of plasma glucose from baseline (week 0) to 156 weeks. The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three.
Time frame: week 0, week 156
Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156 | -11.01 mg/dL | Standard Error 2.11 |
| Lira 1.2 | Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156 | -7.53 mg/dL | Standard Error 2.14 |
| Glimepiride | Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156 | -7.97 mg/dL | Standard Error 2.07 |
Comparison: Change in prandial increments of plasma glucose from baseline to end of treatment at 156 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline value as covariate.p-value: 0.274995% CI: [-8.51, 2.42]ANCOVA
Comparison: Change in prandial increments of plasma glucose from baseline to end of treatment at 156 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline value as covariate.p-value: 0.876595% CI: [-5.05, 5.92]ANCOVA
Comparison: Change in prandial increments of plasma glucose from baseline to end of treatment at 156 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline value as covariate.p-value: 0.208895% CI: [-8.9, 1.95]ANCOVA
Secondary
Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52
Change in mean prandial increments of plasma glucose from baseline (week 0) to 52 weeks (end of double-blind period). The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three.
Time frame: week 0, week 52
Population: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 1.8 | Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52 | -9.6 mg/dL | Standard Error 2.07 |
| Lira 1.2 | Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52 | -8.4 mg/dL | Standard Error 2.1 |
| Glimepiride | Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52 | -5.6 mg/dL | Standard Error 2.04 |
Comparison: Change in mean prandial increments of plasma glucose from baseline to end of treatment at 52 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline value as covariate.p-value: 0.139695% CI: [-9.4, 1.3]ANCOVA
Comparison: Change in mean prandial increments of plasma glucose from baseline to end of treatment at 52 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline value as covariate.p-value: 0.296895% CI: [-8.3, 2.5]ANCOVA
Comparison: Change in postprandial (PPG) from baseline to end of treatment at 52 weeks was analysed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline value as covariate.p-value: 0.663995% CI: [-6.5, 4.1]ANCOVA
Secondary
Hypoglycaemic Episodes
Total number of hypoglycaemic episodes occuring from baseline (week 0) to 104 weeks (end of the 52-week extension). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. 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 0-104
Population: Full safety analysis set is all subjects who had been exposed to at least one dose of the study products.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lira 1.8 | Hypoglycaemic Episodes | Minor | 71 episodes |
| Lira 1.8 | Hypoglycaemic Episodes | Major | 1 episodes |
| Lira 1.8 | Hypoglycaemic Episodes | Symptoms only | 87 episodes |
| Lira 1.2 | Hypoglycaemic Episodes | Minor | 68 episodes |
| Lira 1.2 | Hypoglycaemic Episodes | Major | 0 episodes |
| Lira 1.2 | Hypoglycaemic Episodes | Symptoms only | 133 episodes |
| Glimepiride | Hypoglycaemic Episodes | Major | 0 episodes |
| Glimepiride | Hypoglycaemic Episodes | Symptoms only | 405 episodes |
| Glimepiride | Hypoglycaemic Episodes | Minor | 533 episodes |
Secondary
Hypoglycaemic Episodes
Total number of hypoglycaemic episodes occuring from week 104 to end of trial (week 195). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. 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 104-195
Population: Safety analysis set is all subjects who entered the year 3 extension at week 104.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lira 1.8 | Hypoglycaemic Episodes | Minor | 13 episodes |
| Lira 1.8 | Hypoglycaemic Episodes | Major | 0 episodes |
| Lira 1.8 | Hypoglycaemic Episodes | Symptoms only | 3 episodes |
| Lira 1.2 | Hypoglycaemic Episodes | Minor | 3 episodes |
| Lira 1.2 | Hypoglycaemic Episodes | Major | 0 episodes |
| Lira 1.2 | Hypoglycaemic Episodes | Symptoms only | 1 episodes |
| Glimepiride | Hypoglycaemic Episodes | Major | 1 episodes |
| Glimepiride | Hypoglycaemic Episodes | Symptoms only | 4 episodes |
| Glimepiride | Hypoglycaemic Episodes | Minor | 34 episodes |