Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Japan. The trial aims for comparison of the effect on glycaemic control of liraglutide in combination with sulphonylurea agent (SU) compared to SU monotherapy, as assessed by HbA1c after 24 weeks and 52 weeks in subjects with type 2 diabetes. Liraglutide will be compared to placebo, in combination with SU. Trial has a randomisation period of 24 weeks followed by a 28 week extension period, in total 52 weeks.
Interventions
DRUGsulfonylurea
SU agent
DRUGliraglutide
Liraglutide 0.6 mg/day or placebo. Injected s.c. (under the skin) once 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
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes * Diet/exercise therapy with sulfonylurea (SU) for at least eight weeks * HbA1c greater than or equal to 7.0% and less than 10.0% * BMI less than 35 kg/m2
Exclusion criteria
* Treatment with insulin within the last 12 weeks * Treatment with any drug that could interfere with the glucose level * Any serious medical condition * Females who are pregnant, have intention of becoming pregnant or are breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Glycosylated Haemoglobin A1c (HbA1c) After 24 Weeks of Treatment | after 24 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Plasma Glucose After 24 Weeks of Treatment | after 24 weeks of treatment | — |
| Fasting Plasma Glucose After 52 Weeks of Treatment | after 52 weeks of treatment | — |
| Postprandial Glucose AUC After 24 Weeks of Treatment | after 24 weeks of treatment | Postprandial glucose AUC measured 0-3 hours after a meal after 24 weeks of treatment |
| Postprandial Glucose AUC After 52 Weeks of Treatment | after 52 weeks of treatment | Postprandial Glucose AUC measured 0-3 hours after a meal after 52 weeks of treatment |
| Mean PG in 7-point Plasma Glucose Profile After 24 Weeks of Treatment | after 24 weeks of treatment | Plasma glucose (PG) profile measured after 24 weeks of treatment. The 7 time points during the day were: Before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, and at bedtime. |
| Glycosylated Haemoglobin A1c (HbA1c) After 52 Weeks of Treatment | after 52 weeks of treatment | — |
| Mean Postprandial PG Increment in 7-point Plasma Glucose Profile After 24 Weeks of Treatment | after 24 weeks of treatment | Mean postprandial plasma glucose (PG) increment in 7-point plasma glucose profile, ie the mean of the difference of plasma glucose measured before and after a meal, after 24 weeks of treatment. The 7 time points during the day were: Before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, and at bedtime. |
| Mean Postprandial PG Increment in 7-point Plasma Glucose Profile After 52 Weeks of Treatment | after 52 weeks of treatment | Mean postprandial plasma glucose (PG) increment in 7-point plasma glucose profile, ie the mean of the difference of plasma glucose measured before and after a meal, after 52 weeks of treatment. The 7 time points during the day were: Before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, and at bedtime. |
| Body Weight After 24 Weeks of Treatment | after 24 weeks of treatment | — |
| Body Weight After 52 Weeks of Treatment | after 52 weeks of treatment | — |
| Hypoglycaemic Episodes | over 52 weeks of treatment | Hypoglycaemic episodes measured over 52 weeks of treatment. 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 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. |
| Mean PG in 7-point Plasma Glucose Profile After 52 Weeks of Treatment | after 52 weeks of treatment | 7-point plasma glucose (PG) profile measured after 52 weeks of treatment. The 7 time points during the day were: Before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, and at bedtime. |
Countries
Japan
Participant flow
Recruitment details
49 sites in Japan
Pre-assignment details
Subjects included were patients with type 2 diabetes treated with diet therapy and one sulphonylurea (SU) agent (glibenclamide, gliclazide or glimepiride). Subjects continued their current SU therapy with, as a rule, no change in the dose and dosage in the study. A total of 267 subjects were randomised, 3 subjects were not exposed to study drug.
Participants by arm
| Arm | Count |
|---|---|
| 0.6 mg + SU Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment | 88 |
| 0.9 mg + SU Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment | 88 |
| SU Mono Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment | 88 |
| Total | 264 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 | 2 |
| Overall Study | Difficultulty in use of device | 0 | 0 | 1 |
| Overall Study | Hypoglycaemia | 2 | 1 | 0 |
| Overall Study | Lack of Efficacy | 2 | 0 | 17 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Subject decision | 0 | 0 | 1 |
| Overall Study | Unable to visit site on schedule | 1 | 0 | 0 |
| Overall Study | Withdrawal of consent | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 0.6 mg + SU | 0.9 mg + SU | SU Mono | Total |
|---|---|---|---|---|
| Age, Continuous | 59.1 years STANDARD_DEVIATION 10.3 | 61.3 years STANDARD_DEVIATION 11 | 58.6 years STANDARD_DEVIATION 9.7 | 59.7 years STANDARD_DEVIATION 10.4 |
| Age, Customized 20-29 | 0 participants | 1 participants | 0 participants | 1 participants |
| Age, Customized 30-39 | 2 participants | 4 participants | 0 participants | 6 participants |
| Age, Customized 40-49 | 16 participants | 5 participants | 19 participants | 40 participants |
| Age, Customized 50-59 | 24 participants | 27 participants | 28 participants | 79 participants |
| Age, Customized 60-69 | 30 participants | 32 participants | 30 participants | 92 participants |
| Age, Customized 70- | 16 participants | 19 participants | 11 participants | 46 participants |
| BMI | 25.25 kg/m2 STANDARD_DEVIATION 3.58 | 24.40 kg/m2 STANDARD_DEVIATION 3.37 | 24.94 kg/m2 STANDARD_DEVIATION 3.96 | 24.86 kg/m2 STANDARD_DEVIATION 3.65 |
| Body weight | 66.19 kg STANDARD_DEVIATION 12.03 | 64.53 kg STANDARD_DEVIATION 11.95 | 66.79 kg STANDARD_DEVIATION 13.66 | 65.84 kg STANDARD_DEVIATION 12.56 |
| Duration of diabetes | 9.33 years STANDARD_DEVIATION 5.77 | 11.61 years STANDARD_DEVIATION 7.68 | 10.06 years STANDARD_DEVIATION 7.28 | 10.33 years STANDARD_DEVIATION 7 |
| HbA1c | 8.48 percentage of total haemoglobin STANDARD_DEVIATION 0.73 | 8.26 percentage of total haemoglobin STANDARD_DEVIATION 0.71 | 8.44 percentage of total haemoglobin STANDARD_DEVIATION 0.83 | 8.39 percentage of total haemoglobin STANDARD_DEVIATION 0.76 |
| Sex: Female, Male Female | 35 Participants | 29 Participants | 31 Participants | 95 Participants |
| Sex: Female, Male Male | 53 Participants | 59 Participants | 57 Participants | 169 Participants |
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 | 68 / 88 | 68 / 88 | 59 / 88 |
| serious Total, serious adverse events | 4 / 88 | 3 / 88 | 5 / 88 |
Outcome results
Primary
Glycosylated Haemoglobin A1c (HbA1c) After 24 Weeks of Treatment
Time frame: after 24 weeks of treatment
Population: Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg + SU | Glycosylated Haemoglobin A1c (HbA1c) After 24 Weeks of Treatment | 7.02 percentage of total haemoglobin | Standard Error 0.1 |
| 0.9 mg + SU | Glycosylated Haemoglobin A1c (HbA1c) After 24 Weeks of Treatment | 6.75 percentage of total haemoglobin | Standard Error 0.11 |
| SU Mono | Glycosylated Haemoglobin A1c (HbA1c) After 24 Weeks of Treatment | 8.02 percentage of total haemoglobin | Standard Error 0.1 |
Comparison: ANOVA model included treatment group and pre-trial SU as fixed effects and HbA1C at baseline as a covariate. Two null hypotheses were statistically tested:~H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively. When the test of comparison between 0.9 mg+SU and SU mono was significant, the test of comparison between 0.6 mg+SU and SU mono was performed.p-value: <0.000195% CI: [-1.51, 1.02]ANOVA
Comparison: ANOVA model included treatment group and pre-trial SU as fixed effects and HbA1C at baseline as a covariate. Two null hypotheses were statistically tested:~H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively. When the test of comparison between 0.9 mg+SU and SU mono was significant, the test of comparison between 0.6 mg+SU and SU mono was performed.p-value: <0.000195% CI: [-1.24, -0.75]ANOVA
Secondary
Body Weight After 24 Weeks of Treatment
Time frame: after 24 weeks of treatment
Population: Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg + SU | Body Weight After 24 Weeks of Treatment | 65.77 kg | Standard Error 0.23 |
| 0.9 mg + SU | Body Weight After 24 Weeks of Treatment | 65.34 kg | Standard Error 0.24 |
| SU Mono | Body Weight After 24 Weeks of Treatment | 64.59 kg | Standard Error 0.23 |
Comparison: ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%:~H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.p-value: 0.007195% CI: [0.21, 1.3]ANOVA
Comparison: ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%:~H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.p-value: <0.000195% CI: [0.63, 1.73]ANOVA
Secondary
Body Weight After 52 Weeks of Treatment
Time frame: after 52 weeks of treatment
Population: Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg + SU | Body Weight After 52 Weeks of Treatment | 65.96 kg | Standard Error 0.26 |
| 0.9 mg + SU | Body Weight After 52 Weeks of Treatment | 65.87 kg | Standard Error 0.27 |
| SU Mono | Body Weight After 52 Weeks of Treatment | 64.83 kg | Standard Error 0.26 |
Comparison: 95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.95% CI: [0.42, 1.66]ANOVA
Comparison: 95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed95% CI: [0.51, 1.75]ANOVA
Secondary
Fasting Plasma Glucose After 24 Weeks of Treatment
Time frame: after 24 weeks of treatment
Population: Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg + SU | Fasting Plasma Glucose After 24 Weeks of Treatment | 132.2 mg/dL | Standard Error 3.5 |
| 0.9 mg + SU | Fasting Plasma Glucose After 24 Weeks of Treatment | 126.2 mg/dL | Standard Error 3.5 |
| SU Mono | Fasting Plasma Glucose After 24 Weeks of Treatment | 158.8 mg/dL | Standard Error 3.5 |
Comparison: ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%: H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.p-value: <0.000195% CI: [-40.5, -24.2]ANOVA
Comparison: ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%: H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.p-value: <0.000195% CI: [-34.5, -18.2]ANOVA
Secondary
Fasting Plasma Glucose After 52 Weeks of Treatment
Time frame: after 52 weeks of treatment
Population: Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg + SU | Fasting Plasma Glucose After 52 Weeks of Treatment | 140.3 mg/dL | Standard Error 4 |
| 0.9 mg + SU | Fasting Plasma Glucose After 52 Weeks of Treatment | 134.5 mg/dL | Standard Error 4.1 |
| SU Mono | Fasting Plasma Glucose After 52 Weeks of Treatment | 164.6 mg/dL | Standard Error 4 |
Comparison: 95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.95% CI: [-39.6, -20.7]ANOVA
Comparison: 95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.95% CI: [-33.8, -14.9]ANOVA
Secondary
Glycosylated Haemoglobin A1c (HbA1c) After 52 Weeks of Treatment
Time frame: after 52 weeks of treatment
Population: Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg + SU | Glycosylated Haemoglobin A1c (HbA1c) After 52 Weeks of Treatment | 7.42 percentage of total haemoglobin | Standard Error 0.12 |
| 0.9 mg + SU | Glycosylated Haemoglobin A1c (HbA1c) After 52 Weeks of Treatment | 7.06 percentage of total haemoglobin | Standard Error 0.13 |
| SU Mono | Glycosylated Haemoglobin A1c (HbA1c) After 52 Weeks of Treatment | 8.39 percentage of total haemoglobin | Standard Error 0.12 |
Comparison: 95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.95% CI: [-1.62, -1.04]ANOVA
Comparison: 95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.95% CI: [-1.25, -0.67]ANOVA
Secondary
Hypoglycaemic Episodes
Hypoglycaemic episodes measured over 52 weeks of treatment. 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 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.
Time frame: over 52 weeks of treatment
Population: Full Analysis Set (FAS) consists of all subjects who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 0.6 mg + SU | Hypoglycaemic Episodes | All hypoglycaemic episodes | 3.131 number of events per year of exposure |
| 0.6 mg + SU | Hypoglycaemic Episodes | Major | 0.0000 number of events per year of exposure |
| 0.6 mg + SU | Hypoglycaemic Episodes | Minor | 1.438 number of events per year of exposure |
| 0.6 mg + SU | Hypoglycaemic Episodes | Symptoms only | 1.693 number of events per year of exposure |
| 0.9 mg + SU | Hypoglycaemic Episodes | Symptoms only | 2.350 number of events per year of exposure |
| 0.9 mg + SU | Hypoglycaemic Episodes | All hypoglycaemic episodes | 3.715 number of events per year of exposure |
| 0.9 mg + SU | Hypoglycaemic Episodes | Minor | 1.365 number of events per year of exposure |
| 0.9 mg + SU | Hypoglycaemic Episodes | Major | 0.0000 number of events per year of exposure |
| SU Mono | Hypoglycaemic Episodes | Symptoms only | 1.705 number of events per year of exposure |
| SU Mono | Hypoglycaemic Episodes | Major | 0.0000 number of events per year of exposure |
| SU Mono | Hypoglycaemic Episodes | Minor | 1.285 number of events per year of exposure |
| SU Mono | Hypoglycaemic Episodes | All hypoglycaemic episodes | 2.990 number of events per year of exposure |
Comparison: The relative risk for 'All hypoglycaemic episodes' and 95% confidence interval are based on a generalised linear negative-binomial model, which included treatment group as a fixed effect and log of exposure time as an offset variable.95% CI: [0.86, 2.96]Negative binomial regression
Comparison: The relative risk for 'Minor episodes' and 95% confidence interval are based on a generalised linear negative-binomial model, which included treatment group as a fixed effect and log of exposure time as an offset variable.95% CI: [0.56, 2.47]Negative binomial regression model
Comparison: The relative risk for 'Symptoms only' and 95% confidence interval are based on a generalised linear negative-binomial model, which included treatment group as a fixed effect and log of exposure time as an offset variable.95% CI: [0.92, 3.54]Negative binomial regression model
Comparison: The relative risk for 'All hypoglycaemic episodes' and 95% confidence interval are based on a generalised linear negative-binomial model, which included treatment group as a fixed effect and log of exposure time as an offset variable.95% CI: [0.85, 3.07]Negative binomial regression model
Comparison: The relative risk for 'Minor episodes' and 95% confidence interval are based on a generalised linear negative-binomial model, which included treatment group as a fixed effect and log of exposure time as an offset variable.95% CI: [0.69, 3.17]Negative binomial regression model
Comparison: The relative risk for 'Symptoms only episodes' and 95% confidence interval are based on a generalised linear negative-binomial model, which included treatment group as a fixed effect and log of exposure time as an offset variable.95% CI: [0.72, 2.91]Negative binomial regression model
Secondary
Mean PG in 7-point Plasma Glucose Profile After 24 Weeks of Treatment
Plasma glucose (PG) profile measured after 24 weeks of treatment. The 7 time points during the day were: Before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, and at bedtime.
Time frame: after 24 weeks of treatment
Population: Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg + SU | Mean PG in 7-point Plasma Glucose Profile After 24 Weeks of Treatment | 160.20 mg/dL | Standard Error 4.44 |
| 0.9 mg + SU | Mean PG in 7-point Plasma Glucose Profile After 24 Weeks of Treatment | 150.05 mg/dL | Standard Error 4.56 |
| SU Mono | Mean PG in 7-point Plasma Glucose Profile After 24 Weeks of Treatment | 194.50 mg/dL | Standard Error 4.61 |
Comparison: ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%:~H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.p-value: <0.000195% CI: [-55.02, -33.89]ANOVA
Comparison: ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%:~H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.p-value: <0.000195% CI: [-45.06, -23.54]ANOVA
Secondary
Mean PG in 7-point Plasma Glucose Profile After 52 Weeks of Treatment
7-point plasma glucose (PG) profile measured after 52 weeks of treatment. The 7 time points during the day were: Before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, and at bedtime.
Time frame: after 52 weeks of treatment
Population: Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg + SU | Mean PG in 7-point Plasma Glucose Profile After 52 Weeks of Treatment | 171.42 mg/dL | Standard Error 5.11 |
| 0.9 mg + SU | Mean PG in 7-point Plasma Glucose Profile After 52 Weeks of Treatment | 159.58 mg/dL | Standard Error 5.3 |
| SU Mono | Mean PG in 7-point Plasma Glucose Profile After 52 Weeks of Treatment | 205.92 mg/dL | Standard Error 5.25 |
Comparison: 95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.95% CI: [-46.77, -22.22]ANOVA
Comparison: 95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.95% CI: [-58.49, -34.18]ANOVA
Secondary
Mean Postprandial PG Increment in 7-point Plasma Glucose Profile After 24 Weeks of Treatment
Mean postprandial plasma glucose (PG) increment in 7-point plasma glucose profile, ie the mean of the difference of plasma glucose measured before and after a meal, after 24 weeks of treatment. The 7 time points during the day were: Before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, and at bedtime.
Time frame: after 24 weeks of treatment
Population: Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg + SU | Mean Postprandial PG Increment in 7-point Plasma Glucose Profile After 24 Weeks of Treatment | 86.38 mg/dL | Standard Error 4.65 |
| 0.9 mg + SU | Mean Postprandial PG Increment in 7-point Plasma Glucose Profile After 24 Weeks of Treatment | 68.34 mg/dL | Standard Error 4.78 |
| SU Mono | Mean Postprandial PG Increment in 7-point Plasma Glucose Profile After 24 Weeks of Treatment | 79.71 mg/dL | Standard Error 4.75 |
Comparison: ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%:~H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.p-value: 0.043395% CI: [-22.4, -0.34]ANOVA
Comparison: ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%:~H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.p-value: 0.235995% CI: [-4.39, 17.73]ANOVA
Secondary
Mean Postprandial PG Increment in 7-point Plasma Glucose Profile After 52 Weeks of Treatment
Mean postprandial plasma glucose (PG) increment in 7-point plasma glucose profile, ie the mean of the difference of plasma glucose measured before and after a meal, after 52 weeks of treatment. The 7 time points during the day were: Before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, and at bedtime.
Time frame: after 52 weeks of treatment
Population: Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg + SU | Mean Postprandial PG Increment in 7-point Plasma Glucose Profile After 52 Weeks of Treatment | 82.28 mg/dL | Standard Error 4.81 |
| 0.9 mg + SU | Mean Postprandial PG Increment in 7-point Plasma Glucose Profile After 52 Weeks of Treatment | 76.09 mg/dL | Standard Error 5 |
| SU Mono | Mean Postprandial PG Increment in 7-point Plasma Glucose Profile After 52 Weeks of Treatment | 89.39 mg/dL | Standard Error 4.86 |
Comparison: 95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.95% CI: [-24.69, -1.9]ANOVA
Comparison: 95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.95% CI: [-18.42, 4.21]ANOVA
Secondary
Postprandial Glucose AUC After 24 Weeks of Treatment
Postprandial glucose AUC measured 0-3 hours after a meal after 24 weeks of treatment
Time frame: after 24 weeks of treatment
Population: Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg + SU | Postprandial Glucose AUC After 24 Weeks of Treatment | 614.58 mg/dL *h | Standard Error 14.75 |
| 0.9 mg + SU | Postprandial Glucose AUC After 24 Weeks of Treatment | 575.50 mg/dL *h | Standard Error 15.01 |
| SU Mono | Postprandial Glucose AUC After 24 Weeks of Treatment | 725.72 mg/dL *h | Standard Error 15.71 |
Comparison: ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%:~H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.p-value: <0.000195% CI: [-186.32, -114.12]ANOVA
Comparison: ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%:~H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.p-value: <0.000195% CI: [-147.61, -74.68]ANOVA
Secondary
Postprandial Glucose AUC After 52 Weeks of Treatment
Postprandial Glucose AUC measured 0-3 hours after a meal after 52 weeks of treatment
Time frame: after 52 weeks of treatment
Population: Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg + SU | Postprandial Glucose AUC After 52 Weeks of Treatment | 648.87 mg/dL *h | Standard Error 16.09 |
| 0.9 mg + SU | Postprandial Glucose AUC After 52 Weeks of Treatment | 589.98 mg/dL *h | Standard Error 16.17 |
| SU Mono | Postprandial Glucose AUC After 52 Weeks of Treatment | 717.55 mg/dL *h | Standard Error 17.08 |
Comparison: 95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.95% CI: [-166.91, -88.24]ANOVA
Comparison: 95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.95% CI: [-108.91, -28.45]ANOVA