Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Europe, Oceania, Africa, Asia and South America. This trial is designed to show the effect of treatment with liraglutide when adding to existing metformin therapy and to compare it with the effects of metformin monotherapy and combination therapy of metformin and glimepiride. Two trial periods: A 6 month (26 weeks) randomised, double-blinded period followed by an 18 months open-label extension, in total 2 years (104 weeks).
Interventions
DRUGliraglutide
0.6 mg for s.c. (under the skin) injection.
DRUGmetformin
1.5-2.0 g tablets
DRUGglimepiride
4 mg tablets
DRUGplacebo
Glimepiride placebo 1 mg and 2 mg tablets
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
* Subjects diagnosed with type 2 diabetes and treated with oral anti-diabetic drugs (OADs) for at least 3 months * HbA1c: 7.0-11.0 % (both incl.) in subjects on OAD monotherapy. 7.0-10.0 % (both incl.) in subjects on OAD combination therapy * Body Mass Index (BMI) less than or equal 40 kg/m2
Exclusion criteria
* Subjects treated with insulin within the last three months * Subjects with any serious medical condition * Females of child bearing potential who are pregnant, breast-feeding or have the intention of becoming pregnant or not using adequate contraceptive methods * Subjects using any drug (except for OADs), which in the Investigator's opinion could interfere with the glucose level (e.g. systemic corticosteroids)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycosylated A1c (HbA1c) at Week 26 | week 0, week 26 | Percentage point change in Glycosylated A1c (HbA1c) from baseline (week 0) to 26 weeks (end of randomisation) |
| Change in Glycosylated A1c (HbA1c) at Week 104 | week 0, week 104 | Change in glycosylated A1c (HbA1c) baseline (week 0) to 104 weeks (end of randomisation) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Plasma Glucose (FPG) at Week 26 | week 0, week 26 | Change in fasting plasma glucose (FPG) from baseline (week 0) to 26 weeks (end of randomisation) |
| Change in Fasting Plasma Glucose (FPG) at Week 104 | week 0, week 104 | Change in Fasting plasma glucose (FPG) from baseline (week 0) to 104 weeks (end of treatment) |
| Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26 | week 0, week 26 | Change in mean prandial increments of plasma glucose based on self-measured 7-point plasma glucose profiles from baseline (week 0) to 26 weeks (end of randomisation). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between values measured before and after a meal (breakfast, lunch and dinner) divided by three. |
| Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104 | week 0, week 104 | Change in mean prandial increments of plasma glucose based on self-measured 7-point plasma glucose profiles from baseline (week 0) to 104 weeks (end of treatment). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between values measured before and after a meal (breakfast, lunch and dinner) divided by three. |
| Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26 | week 0, week 26 | Change in mean post prandial plasma glucose from baseline (Week 0) to 26 weeks (end of randomisation). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime. Mean post prandial plasma glucose were calculated as the sum of the post pradial plasma glucose values divided by three. |
| Change in Body Weight at Week 26 | week 0, week 26 | Change in body weight from baseline (week 0) to 26 weeks (end of randomisation) |
| Change in Beta-cell Function at Week 26 | week 0, week 26 | Change in beta cell function from baseline (week 0) to 16 weeks (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B). Beta-cell function: HOMA-B (%) = 20∙fasting insulin\[uU/mL\] divided by (FPG mmol/L\]-3.5). |
| Change in Beta-cell Function at Week 104 | week 0, week 104 | Change in beta cell function from baseline (week 0) to 16 weeks (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B). Beta-cell function: HOMA-B (%) = 20∙fasting insulin\[uU/mL\] divided by (FPG mmol/L\]-3.5). |
| Hypoglycaemic Episodes at Week 26 | weeks 0-26 | Total number of hypoglycaemic episodes occuring after baseline (week 0) until week 26 (end of randomisation). 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. |
| Hypoglycaemic Episodes at Week 104 | weeks 0-104 | Total number of hypoglycaemic episodes occuring after baseline (week 0) until 104 weeks (end 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. |
| Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104 | week 0, week 104 | Change in mean post prandial plasma glucose from baseline (Week 0) to 104 weeks (end of treatment) The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime. Mean post prandial plasma glucose were calculated as the sum of the post pradial plasma glucose values divided by three. |
| Change in Body Weight at Week 104 | week 0, week 104 | Change in body weight from baseline (week 0) to 104 weeks (end of treatment) |
Countries
Argentina, Australia, Belgium, Bulgaria, Croatia, Denmark, Germany, Hungary, India, Ireland, Italy, Netherlands, Norway, Romania, Russia, Slovakia, South Africa, Spain, Sweden, United Kingdom
Participant flow
Recruitment details
A total of 170 centres in 21 countries: Argentina (4), Australia (19), Belgium (6), Bulgaria (1), Germany (33), Denmark (9), Spain (14), United Kingdom (11), Croatia (2), Hungary (5), Ireland (4), India (5), Italy (10), The Netherlands (5), New Zealand (3), Norway (8), Romania (3), Russia (6), Sweden (8), Slovakia (7) and South Africa (7)
Pre-assignment details
Eligible subjects discontinued their oral anti-diabetic drug treatment and commenced a 3-week period of forced titration of metformin followed by a 3-week maintenance period. Subjects on current metformin therapy could go through a modified titration period or advance directly to the 3-week maintenance period at the discretion of the investigator.
Participants by arm
| Arm | Count |
|---|---|
| Lira 0.6 + Met Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104) | 242 |
| Lira 1.2 + Met Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104) | 240 |
| Lira 1.8 + Met Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104) | 242 |
| Met Mono Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104) | 121 |
| Met + Glim Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104) | 242 |
| Total | 1,087 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Double-Blind, 6 Months | Adverse Event | 11 | 23 | 29 | 2 | 8 |
| Double-Blind, 6 Months | Consent withdrawn | 0 | 3 | 4 | 10 | 4 |
| Double-Blind, 6 Months | Fear of experiencing AE again | 0 | 1 | 0 | 0 | 0 |
| Double-Blind, 6 Months | FPG exceeds limits/too high | 1 | 0 | 0 | 2 | 0 |
| Double-Blind, 6 Months | Hyperglicaemia | 0 | 0 | 0 | 1 | 0 |
| Double-Blind, 6 Months | Hypoglycaemia/Hypoglycemia | 0 | 0 | 0 | 0 | 2 |
| Double-Blind, 6 Months | Investigator decision | 0 | 0 | 0 | 0 | 1 |
| Double-Blind, 6 Months | Lack of Efficacy | 19 | 8 | 13 | 29 | 9 |
| Double-Blind, 6 Months | Lack of time | 1 | 0 | 0 | 0 | 0 |
| Double-Blind, 6 Months | Lost to follow up | 0 | 1 | 0 | 0 | 0 |
| Double-Blind, 6 Months | metformin titrated <1500 mg or >2000 mg | 0 | 0 | 0 | 0 | 1 |
| Double-Blind, 6 Months | Move | 0 | 1 | 0 | 0 | 0 |
| Double-Blind, 6 Months | Poor compliance/Non-compliance | 0 | 1 | 0 | 0 | 0 |
| Double-Blind, 6 Months | Protocol Violation | 2 | 4 | 4 | 4 | 5 |
| Double-Blind, 6 Months | Subject decision/No wish to continue | 0 | 2 | 1 | 0 | 2 |
| Double-Blind, 6 Months | Tendency to low blood glucose levels | 0 | 0 | 0 | 0 | 1 |
| Double-Blind, 6 Months | Work commitment | 0 | 0 | 0 | 0 | 1 |
| Open-Label Extension, 18 Months | Adverse Event | 11 | 8 | 6 | 1 | 6 |
| Open-Label Extension, 18 Months | Lack of Efficacy | 41 | 33 | 37 | 27 | 63 |
| Open-Label Extension, 18 Months | Protocol Violation | 7 | 5 | 3 | 4 | 6 |
| Open-Label Extension, 18 Months | Withdrawals between 6 and 24 months | 19 | 14 | 27 | 11 | 22 |
Baseline characteristics
| Characteristic | Lira 0.6 + Met | Total | Met + Glim | Met Mono | Lira 1.8 + Met | Lira 1.2 + Met |
|---|---|---|---|---|---|---|
| Age, Continuous | 56.0 years STANDARD_DEVIATION 10.5 | 56.7 years STANDARD_DEVIATION 9.5 | 57.3 years STANDARD_DEVIATION 8.8 | 56.0 years STANDARD_DEVIATION 9.4 | 56.8 years STANDARD_DEVIATION 9.4 | 57.2 years STANDARD_DEVIATION 9.2 |
| BMI | 30.5 kg/m2 STANDARD_DEVIATION 4.8 | 31.0 kg/m2 STANDARD_DEVIATION 4.7 | 31.2 kg/m2 STANDARD_DEVIATION 4.6 | 31.6 kg/m2 STANDARD_DEVIATION 4.4 | 30.9 kg/m2 STANDARD_DEVIATION 4.6 | 31.1 kg/m2 STANDARD_DEVIATION 4.8 |
| Duration of diabetes | 7.0 years STANDARD_DEVIATION 4.8 | 7.4 years STANDARD_DEVIATION 5.2 | 7.7 years STANDARD_DEVIATION 5.3 | 7.9 years STANDARD_DEVIATION 6 | 7.8 years STANDARD_DEVIATION 5.2 | 6.8 years STANDARD_DEVIATION 4.9 |
| HbA1c | 8.4 percentage of total haemoglobin STANDARD_DEVIATION 0.9 | 8.4 percentage of total haemoglobin STANDARD_DEVIATION 0.9 | 8.4 percentage of total haemoglobin STANDARD_DEVIATION 0.9 | 8.4 percentage of total haemoglobin STANDARD_DEVIATION 1 | 8.3 percentage of total haemoglobin STANDARD_DEVIATION 0.9 | 8.3 percentage of total haemoglobin STANDARD_DEVIATION 0.9 |
| Height | 1.69 m STANDARD_DEVIATION 0.1 | 1.69 m STANDARD_DEVIATION 0.1 | 1.69 m STANDARD_DEVIATION 0.11 | 1.69 m STANDARD_DEVIATION 0.1 | 1.69 m STANDARD_DEVIATION 0.1 | 1.68 m STANDARD_DEVIATION 0.11 |
| Previous anti-diabetic treatment Combination therapy | 161 participants | 703 participants | 152 participants | 80 participants | 160 participants | 150 participants |
| Previous anti-diabetic treatment Mono-therapy | 81 participants | 384 participants | 90 participants | 41 participants | 82 participants | 90 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 31 Participants | 98 Participants | 21 Participants | 9 Participants | 18 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 26 Participants | 5 Participants | 3 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 17 Participants | 2 Participants | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) White | 202 Participants | 946 Participants | 214 Participants | 106 Participants | 214 Participants | 210 Participants |
| Sex: Female, Male Female | 91 Participants | 454 Participants | 103 Participants | 49 Participants | 100 Participants | 111 Participants |
| Sex: Female, Male Male | 151 Participants | 633 Participants | 139 Participants | 72 Participants | 142 Participants | 129 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 132 / 242 | 144 / 240 | 158 / 242 | 44 / 121 | 128 / 242 |
| serious Total, serious adverse events | 36 / 242 | 25 / 240 | 16 / 242 | 9 / 121 | 24 / 242 |
Outcome results
Primary
Change in Glycosylated A1c (HbA1c) at Week 104
Change in glycosylated A1c (HbA1c) baseline (week 0) to 104 weeks (end of randomisation)
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 0.6 + Met | Change in Glycosylated A1c (HbA1c) at Week 104 | -0.36 percentage of total haemoglobin | Standard Error 0.08 |
| Lira 1.2 + Met | Change in Glycosylated A1c (HbA1c) at Week 104 | -0.56 percentage of total haemoglobin | Standard Error 0.08 |
| Lira 1.8 + Met | Change in Glycosylated A1c (HbA1c) at Week 104 | -0.58 percentage of total haemoglobin | Standard Error 0.08 |
| Met Mono | Change in Glycosylated A1c (HbA1c) at Week 104 | 0.25 percentage of total haemoglobin | Standard Error 0.1 |
| Met + Glim | Change in Glycosylated A1c (HbA1c) at Week 104 | -0.50 percentage of total haemoglobin | Standard Error 0.08 |
Comparison: Change in HbA1c from baseline to end of treatment at 104 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline glycosylated A1c (HbA1c) as covariate.p-value: <0.000195% CI: [-1.07, -0.59]ANCOVA
Comparison: Change in HbA1c from baseline to end of treatment at 104 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline glycosylated A1c (HbA1c) as covariate.p-value: <0.000195% CI: [-0.28, 0.12]ANCOVA
Comparison: Change in HbA1c from baseline to end of treatment was at 104 weeks analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline glycosylated A1c (HbA1c) as covariate.p-value: <0.000195% CI: [-1.05, -0.57]ANCOVA
Comparison: Change in HbA1c from baseline to end of treatment at 104 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline glycosylated A1c (HbA1c) as covariate.p-value: <0.000195% CI: [-0.27, 0.13]ANCOVA
Comparison: Change in HbA1c from baseline to end of treatment at 104 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline glycosylated A1c (HbA1c) as covariate.p-value: <0.000195% CI: [-0.85, -0.37]ANCOVA
Comparison: Change in HbA1c from baseline to end of treatment at 104 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline glycosylated A1c (HbA1c) as covariate.p-value: 0.005295% CI: [-0.06, 0.34]ANCOVA
Comparison: Change in HbA1c from baseline to end of treatment at 104 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline glycosylated A1c (HbA1c) as covariate.p-value: <0.000195% CI: [-0.99, -0.51]ANCOVA
Primary
Change in Glycosylated A1c (HbA1c) at Week 26
Percentage point change in Glycosylated A1c (HbA1c) from baseline (week 0) to 26 weeks (end of randomisation)
Time frame: week 0, week 26
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 0.6 + Met | Change in Glycosylated A1c (HbA1c) at Week 26 | -0.69 Percentage point of total HbA1c | Standard Error 0.07 |
| Lira 1.2 + Met | Change in Glycosylated A1c (HbA1c) at Week 26 | -0.97 Percentage point of total HbA1c | Standard Error 0.07 |
| Lira 1.8 + Met | Change in Glycosylated A1c (HbA1c) at Week 26 | -1.00 Percentage point of total HbA1c | Standard Error 0.07 |
| Met Mono | Change in Glycosylated A1c (HbA1c) at Week 26 | 0.09 Percentage point of total HbA1c | Standard Error 0.09 |
| Met + Glim | Change in Glycosylated A1c (HbA1c) at Week 26 | -0.98 Percentage point of total HbA1c | Standard Error 0.07 |
Comparison: Change in HbA1c from baseline to end of treatment at 26 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline glycosylated A1c (HbA1c) as covariate.p-value: <0.000195% CI: [-1.3, -0.88]ANCOVA
Comparison: Change in HbA1c from baseline to end of treatment at 26 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline glycosylated A1c (HbA1c) as covariate.p-value: <0.000195% CI: [-0.19, 0.15]ANCOVA
Comparison: Change in HbA1c from baseline to end of treatment at 26 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline glycosylated A1c (HbA1c) as covariate.p-value: <0.000195% CI: [-1.27, -0.85]ANCOVA
Comparison: Change in HbA1c from baseline to end of treatment at 26 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline glycosylated A1c (HbA1c) as covariate.p-value: <0.000195% CI: [-0.16, 0.18]ANCOVA
Comparison: Change in HbA1c from baseline to end of treatment at 26 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline glycosylated A1c (HbA1c) as covariate.p-value: <0.000195% CI: [-0.99, -0.57]ANCOVA
Comparison: Change in HbA1c from baseline to end of treatment at 26 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline glycosylated A1c (HbA1c) as covariate.p-value: 0.102695% CI: [0.12, 0.46]ANCOVA
Comparison: Change in HbA1c from baseline to end of treatment at 26 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline glycosylated A1c (HbA1c) as covariate.p-value: <0.000195% CI: [-1.28, -0.86]ANCOVA
Secondary
Change in Beta-cell Function at Week 104
Change in beta cell function from baseline (week 0) to 16 weeks (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B). Beta-cell function: HOMA-B (%) = 20∙fasting insulin\[uU/mL\] divided by (FPG mmol/L\]-3.5).
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 0.6 + Met | Change in Beta-cell Function at Week 104 | 64.48 percentage point (%point) | Standard Error 24.93 |
| Lira 1.2 + Met | Change in Beta-cell Function at Week 104 | 27.30 percentage point (%point) | Standard Error 25.7 |
| Lira 1.8 + Met | Change in Beta-cell Function at Week 104 | 17.81 percentage point (%point) | Standard Error 25.03 |
| Met Mono | Change in Beta-cell Function at Week 104 | -7.89 percentage point (%point) | Standard Error 34.47 |
| Met + Glim | Change in Beta-cell Function at Week 104 | 11.25 percentage point (%point) | Standard Error 25.27 |
Comparison: Change in HOMA-B from baseline to 104 weeks of treatment was analyzed 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: 0.882195% CI: [-69.84, 121.26]ANCOVA
Comparison: Change in HOMA-B from baseline to 104 weeks of treatment was analyzed 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: 0.998995% CI: [-72.66, 85.79]ANCOVA
Comparison: Change in HOMA-B from baseline to 104 weeks of treatment was analyzed 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: 0.729295% CI: [-60.33, 130.72]ANCOVA
Comparison: Change in HOMA-B from baseline to 104 weeks of treatment was analyzed 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: 0.968995% CI: [-63.69, 95.79]ANCOVA
Comparison: Change in HOMA-B from baseline to 104 weeks of treatment was analyzed 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: 0.181895% CI: [-23.15, 167.9]ANCOVA
Comparison: Change in HOMA-B from baseline to 104 weeks of treatment was analyzed 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: 0.297895% CI: [-26.3, 132.76]ANCOVA
Secondary
Change in Beta-cell Function at Week 26
Change in beta cell function from baseline (week 0) to 16 weeks (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B). Beta-cell function: HOMA-B (%) = 20∙fasting insulin\[uU/mL\] divided by (FPG mmol/L\]-3.5).
Time frame: week 0, week 26
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 0.6 + Met | Change in Beta-cell Function at Week 26 | 20.45 percentage point (%point) | Standard Error 5.19 |
| Lira 1.2 + Met | Change in Beta-cell Function at Week 26 | 20.33 percentage point (%point) | Standard Error 5.34 |
| Lira 1.8 + Met | Change in Beta-cell Function at Week 26 | 26.12 percentage point (%point) | Standard Error 5.2 |
| Met Mono | Change in Beta-cell Function at Week 26 | -1.63 percentage point (%point) | Standard Error 7.19 |
| Met + Glim | Change in Beta-cell Function at Week 26 | 24.68 percentage point (%point) | Standard Error 5.25 |
Comparison: Change in HOMA-B from baseline to 26 weeks of treatment was analyzed 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: 0.003195% CI: [7.83, 47.67]ANCOVA
Comparison: Change in HOMA-B from baseline to 26 weeks of treatment was analyzed 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: 0.998795% CI: [-15.03, 17.9]ANCOVA
Comparison: Change in HOMA-B from baseline to 26 weeks of treatment was analyzed 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: 0.026395% CI: [2.04, 41.87]ANCOVA
Comparison: Change in HOMA-B from baseline to 26 weeks of treatment was analyzed 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: 0.922795% CI: [-20.94, 12.22]ANCOVA
Comparison: Change in HOMA-B from baseline to 26 weeks of treatment was analyzed 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: 0.025395% CI: [2.15, 42.01]ANCOVA
Comparison: Change in HOMA-B from baseline to 26 weeks of treatment was analyzed 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: 0.929395% CI: [-20.78, 12.31]ANCOVA
Secondary
Change in Body Weight at Week 104
Change in body weight from baseline (week 0) to 104 weeks (end of treatment)
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 0.6 + Met | Change in Body Weight at Week 104 | -2.07 kg | Standard Error 0.28 |
| Lira 1.2 + Met | Change in Body Weight at Week 104 | -3.03 kg | Standard Error 0.29 |
| Lira 1.8 + Met | Change in Body Weight at Week 104 | -2.91 kg | Standard Error 0.28 |
| Met Mono | Change in Body Weight at Week 104 | -1.80 kg | Standard Error 0.38 |
| Met + Glim | Change in Body Weight at Week 104 | 0.70 kg | Standard Error 0.29 |
Comparison: Change in body weight from baseline to end of treatment at 104 weeks was analyzed 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: 0.037895% CI: [-2.18, -0.05]ANCOVA
Comparison: Change in body weight from baseline to end of treatment at 104 weeks was analyzed 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: [-4.51, -2.72]ANCOVA
Comparison: Change in body weight from baseline to end of treatment at 104 weeks was analyzed 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: 0.018595% CI: [-2.3, -0.16]ANCOVA
Comparison: Change in body weight from baseline to end of treatment at 104 weeks was analyzed 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: [-4.64, -2.83]ANCOVA
Comparison: Change in body weight from baseline to end of treatment at 104 weeks was analyzed 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: 0.906995% CI: [-1.33, 0.8]ANCOVA
Comparison: Change in body weight from baseline to end of treatment at 104 weeks was analyzed 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: [-3.67, -1.87]ANCOVA
Secondary
Change in Body Weight at Week 26
Change in body weight from baseline (week 0) to 26 weeks (end of randomisation)
Time frame: week 0, week 26
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 0.6 + Met | Change in Body Weight at Week 26 | -1.78 kg | Standard Error 0.23 |
| Lira 1.2 + Met | Change in Body Weight at Week 26 | -2.58 kg | Standard Error 0.24 |
| Lira 1.8 + Met | Change in Body Weight at Week 26 | -2.79 kg | Standard Error 0.23 |
| Met Mono | Change in Body Weight at Week 26 | -1.51 kg | Standard Error 0.31 |
| Met + Glim | Change in Body Weight at Week 26 | 0.95 kg | Standard Error 0.23 |
Comparison: Change in body weight from baseline to end of treatment at 26 weeks was analyzed 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: 0.001695% CI: [-2.16, -0.41]ANCOVA
Comparison: Change in body weight from baseline to end of treatment at 26 weeks was analyzed 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: [-4.48, -3.01]ANCOVA
Comparison: Change in body weight from baseline to end of treatment at 26 weeks was analyzed 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: 0.011795% CI: [-1.94, -0.19]ANCOVA
Comparison: Change in body weight from baseline to end of treatment at 26 weeks was analyzed 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: [-4.27, -2.79]ANCOVA
Comparison: Change in body weight from baseline to end of treatment at 26 weeks was analyzed 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: 0.819895% CI: [-1.15, 0.6]ANCOVA
Comparison: Change in body weight from baseline to end of treatment at 26 weeks was analyzed 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: [-3.47, -2]ANCOVA
Secondary
Change in Fasting Plasma Glucose (FPG) at Week 104
Change in Fasting plasma glucose (FPG) from baseline (week 0) to 104 weeks (end of treatment)
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 0.6 + Met | Change in Fasting Plasma Glucose (FPG) at Week 104 | -0.80 mmol/L | Standard Error 0.17 |
| Lira 1.2 + Met | Change in Fasting Plasma Glucose (FPG) at Week 104 | -1.20 mmol/L | Standard Error 0.18 |
| Lira 1.8 + Met | Change in Fasting Plasma Glucose (FPG) at Week 104 | -1.18 mmol/L | Standard Error 0.17 |
| Met Mono | Change in Fasting Plasma Glucose (FPG) at Week 104 | 0.75 mmol/L | Standard Error 0.23 |
| Met + Glim | Change in Fasting Plasma Glucose (FPG) at Week 104 | -0.64 mmol/L | Standard Error 0.17 |
Comparison: Change in fasting plasma glucose from baseline to end of treatment at 104 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline fasting plasma glucose as covariate.p-value: <0.000195% CI: [-2.58, -1.28]ANCOVA
Comparison: Change in fasting plasma glucose from baseline to end of treatment at 104 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline fasting plasma glucose as covariate.p-value: 0.054295% CI: [-1.08, 0.01]ANCOVA
Comparison: Change in fasting plasma glucose from baseline to end of treatment at 104 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline fasting plasma glucose as covariate.p-value: <0.000195% CI: [-2.6, -1.3]ANCOVA
Comparison: Change in fasting plasma glucose from baseline to end of treatment at 104 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline fasting plasma glucose t as covariate.p-value: 0.045195% CI: [-1.1, -0.01]ANCOVA
Comparison: Change in fasting plasma glucose from baseline to end of treatment at 104 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline fasting plasma glucose as covariate.p-value: <0.000195% CI: [-2.2, -0.9]ANCOVA
Comparison: Change in fasting plasma glucose from baseline to end of treatment at 104 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline fasting plasma glucose as covariate.p-value: 0.900695% CI: [-0.7, 0.39]ANCOVA
Secondary
Change in Fasting Plasma Glucose (FPG) at Week 26
Change in fasting plasma glucose (FPG) from baseline (week 0) to 26 weeks (end of randomisation)
Time frame: week 0, week 26
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 0.6 + Met | Change in Fasting Plasma Glucose (FPG) at Week 26 | -1.13 mmol/L | Standard Error 0.15 |
| Lira 1.2 + Met | Change in Fasting Plasma Glucose (FPG) at Week 26 | -1.63 mmol/L | Standard Error 0.16 |
| Lira 1.8 + Met | Change in Fasting Plasma Glucose (FPG) at Week 26 | -1.68 mmol/L | Standard Error 0.15 |
| Met Mono | Change in Fasting Plasma Glucose (FPG) at Week 26 | 0.40 mmol/L | Standard Error 0.21 |
| Met + Glim | Change in Fasting Plasma Glucose (FPG) at Week 26 | -1.31 mmol/L | Standard Error 0.16 |
Comparison: Change in fasting plasma glucose from baseline to end of treatment at 26 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline fasting plasma glucose as covariate.p-value: <0.000195% CI: [-2.68, -1.5]ANCOVA
Comparison: Change in fasting plasma glucose from baseline to end of treatment at 26 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline fasting plasma glucose as covariate.p-value: 0.184595% CI: [-0.87, 0.11]ANCOVA
Comparison: Change in fasting plasma glucose from baseline to end of treatment at 26 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline fasting plasma glucose as covariate.p-value: <0.000195% CI: [-2.63, -1.44]ANCOVA
Comparison: Change in fasting plasma glucose from baseline to end of treatment at 26 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline fasting plasma glucose t as covariate.p-value: 0.304795% CI: [-0.82, 0.17]ANCOVA
Comparison: Change in fasting plasma glucose from baseline to end of treatment at 26 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline fasting plasma glucose as covariate.p-value: <0.000195% CI: [-2.12, -0.94]ANCOVA
Comparison: Change in fasting plasma glucose from baseline to end of treatment at 26 weeks was analyzed using an analysis of covariance (ANCOVA) model with treatment, country and previous anti-diabetic treatment as fixed effects and baseline fasting plasma glucose as covariate.p-value: 0.807995% CI: [-0.32, 0.67]ANCOVA
Secondary
Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104
Change in mean post prandial plasma glucose from baseline (Week 0) to 104 weeks (end of treatment) The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime. Mean post prandial plasma glucose were calculated as the sum of the post pradial plasma glucose values 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 0.6 + Met | Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104 | -1.59 mmol/L | Standard Error 0.18 |
| Lira 1.2 + Met | Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104 | -2.22 mmol/L | Standard Error 0.18 |
| Lira 1.8 + Met | Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104 | -2.10 mmol/L | Standard Error 0.18 |
| Met Mono | Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104 | -0.43 mmol/L | Standard Error 0.26 |
| Met + Glim | Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104 | -1.80 mmol/L | Standard Error 0.18 |
Comparison: Change in post prandial increments of plasma glucose from baseline to 104 weeks of treatment was analyzed 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: <0.000195% CI: [-2.37, -0.96]ANCOVA
Comparison: Change in post prandial increments of plasma glucose from baseline to 104 weeks of treatment was analyzed 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: 0.504895% CI: [-0.86, 0.26]ANCOVA
Comparison: Change in post prandial increments of plasma glucose from baseline to 104 weeks of treatment was analyzed 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: <0.000195% CI: [-2.49, -1.08]ANCOVA
Comparison: Change in post prandial increments of plasma glucose from baseline to 104 weeks of treatment was analyzed 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: 0.200595% CI: [-0.98, 0.14]ANCOVA
Comparison: Change in post prandial increments of plasma glucose from baseline to 104 weeks of treatment was analyzed 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: 0.000395% CI: [-1.86, -0.46]ANCOVA
Comparison: Change in post prandial increments of plasma glucose from baseline to 104 weeks of treatment was analyzed 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: 0.787195% CI: [-0.35, 0.76]ANCOVA
Secondary
Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26
Change in mean post prandial plasma glucose from baseline (Week 0) to 26 weeks (end of randomisation). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime. Mean post prandial plasma glucose were calculated as the sum of the post pradial plasma glucose values divided by three.
Time frame: week 0, week 26
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 0.6 + Met | Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26 | -1.68 mmol/L | Standard Error 0.16 |
| Lira 1.2 + Met | Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26 | -2.33 mmol/L | Standard Error 0.17 |
| Lira 1.8 + Met | Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26 | -2.57 mmol/L | Standard Error 0.16 |
| Met Mono | Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26 | -0.62 mmol/L | Standard Error 0.24 |
| Met + Glim | Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26 | -2.46 mmol/L | Standard Error 0.16 |
Comparison: Change in post prandial increments of plasma glucose from baseline to 26 weeks of treatment was analyzed 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: <0.000195% CI: [-2.6, -1.3]ANCOVA
Comparison: Change in post prandial increments of plasma glucose from baseline to 26 weeks of treatment was analyzed 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: 0.96795% CI: [-0.62, 0.41]ANCOVA
Comparison: Change in post prandial increments of plasma glucose from baseline to 26 weeks of treatment was analyzed 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: <0.000195% CI: [-2.36, -1.07]ANCOVA
Comparison: Change in post prandial increments of plasma glucose from baseline to 26 weeks of treatment was analyzed 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: 0.936895% CI: [-0.39, 0.64]ANCOVA
Comparison: Change in post prandial increments of plasma glucose from baseline to 26 weeks of treatment was analyzed 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: 0.000395% CI: [-1.71, -0.42]ANCOVA
Comparison: Change in post prandial increments of plasma glucose from baseline to 26 weeks of treatment was analyzed 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: 0.000895% CI: [0.27, 1.29]ANCOVA
Secondary
Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104
Change in mean prandial increments of plasma glucose based on self-measured 7-point plasma glucose profiles from baseline (week 0) to 104 weeks (end of treatment). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between values measured before and after a meal (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 0.6 + Met | Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104 | -0.27 mmol/L | Standard Error 0.12 |
| Lira 1.2 + Met | Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104 | -0.56 mmol/L | Standard Error 0.13 |
| Lira 1.8 + Met | Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104 | -0.44 mmol/L | Standard Error 0.13 |
| Met Mono | Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104 | -0.20 mmol/L | Standard Error 0.18 |
| Met + Glim | Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104 | -0.29 mmol/L | Standard Error 0.13 |
Comparison: Change in prandial increments of plasma glucose from baseline to 104 weeks of treatment was analyzed 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: 0.528295% CI: [-0.74, 0.26]ANCOVA
Comparison: Change in prandial increments of plasma glucose from baseline to 104 weeks of treatment was analyzed 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: 0.764495% CI: [-0.55, 0.25]ANCOVA
Comparison: Change in prandial increments of plasma glucose from baseline to 104 weeks of treatment was analyzed 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: 0.206395% CI: [-0.86, 0.14]ANCOVA
Comparison: Change in prandial increments of plasma glucose from baseline to 104 weeks of treatment was analyzed 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: 0.267895% CI: [-0.68, 0.12]ANCOVA
Comparison: Change in prandial increments of plasma glucose from baseline to 104 weeks of treatment was analyzed 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: 0.988795% CI: [-0.57, 0.43]ANCOVA
Comparison: Change in prandial increments of plasma glucose from baseline to 104 weeks of treatment was analyzed 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: 0.999895% CI: [-0.38, 0.42]ANCOVA
Secondary
Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26
Change in mean prandial increments of plasma glucose based on self-measured 7-point plasma glucose profiles from baseline (week 0) to 26 weeks (end of randomisation). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between values measured before and after a meal (breakfast, lunch and dinner) divided by three.
Time frame: week 0, week 26
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 0.6 + Met | Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26 | -0.23 mmol/l | Standard Error 0.12 |
| Lira 1.2 + Met | Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26 | -0.40 mmol/l | Standard Error 0.13 |
| Lira 1.8 + Met | Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26 | -0.56 mmol/l | Standard Error 0.12 |
| Met Mono | Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26 | -0.44 mmol/l | Standard Error 0.18 |
| Met + Glim | Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26 | -0.44 mmol/l | Standard Error 0.12 |
Comparison: Change in prandial increments of plasma glucose from baseline to 26 weeks of treatment was analyzed 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: 0.887195% CI: [-0.62, 0.36]ANCOVA
Comparison: Change in prandial increments of plasma glucose from baseline to 26 weeks of treatment was analyzed 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: 0.869595% CI: [-0.51, 0.27]ANCOVA
Comparison: Change in prandial increments of plasma glucose from baseline to 26 weeks of treatment was analyzed 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: 0.999495% CI: [-0.46, 0.52]ANCOVA
Comparison: Change in prandial increments of plasma glucose from baseline to 26 weeks of treatment was analyzed 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: 0.998495% CI: [-0.35, 0.43]ANCOVA
Comparison: Change in mean prandial increments of plasma glucose from baseline to 26 weeks of treatment was analyzed 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: 0.620195% CI: [-0.28, 0.7]ANCOVA
Comparison: Change in mean prandial increments of plasma glucose from baseline to 26 weeks of treatment was analyzed 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: 0.483195% CI: [-0.18, 0.6]ANCOVA
Secondary
Hypoglycaemic Episodes at Week 104
Total number of hypoglycaemic episodes occuring after baseline (week 0) until 104 weeks (end 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: weeks 0-104
Population: Safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lira 0.6 + Met | Hypoglycaemic Episodes at Week 104 | All | 52 episodes |
| Lira 0.6 + Met | Hypoglycaemic Episodes at Week 104 | Major | 0 episodes |
| Lira 0.6 + Met | Hypoglycaemic Episodes at Week 104 | Minor | 23 episodes |
| Lira 0.6 + Met | Hypoglycaemic Episodes at Week 104 | Symptoms only | 29 episodes |
| Lira 1.2 + Met | Hypoglycaemic Episodes at Week 104 | All | 51 episodes |
| Lira 1.2 + Met | Hypoglycaemic Episodes at Week 104 | Symptoms only | 24 episodes |
| Lira 1.2 + Met | Hypoglycaemic Episodes at Week 104 | Major | 1 episodes |
| Lira 1.2 + Met | Hypoglycaemic Episodes at Week 104 | Minor | 26 episodes |
| Lira 1.8 + Met | Hypoglycaemic Episodes at Week 104 | Symptoms only | 27 episodes |
| Lira 1.8 + Met | Hypoglycaemic Episodes at Week 104 | Major | 0 episodes |
| Lira 1.8 + Met | Hypoglycaemic Episodes at Week 104 | Minor | 22 episodes |
| Lira 1.8 + Met | Hypoglycaemic Episodes at Week 104 | All | 49 episodes |
| Met Mono | Hypoglycaemic Episodes at Week 104 | All | 18 episodes |
| Met Mono | Hypoglycaemic Episodes at Week 104 | Major | 0 episodes |
| Met Mono | Hypoglycaemic Episodes at Week 104 | Symptoms only | 12 episodes |
| Met Mono | Hypoglycaemic Episodes at Week 104 | Minor | 6 episodes |
| Met + Glim | Hypoglycaemic Episodes at Week 104 | Symptoms only | 240 episodes |
| Met + Glim | Hypoglycaemic Episodes at Week 104 | Minor | 284 episodes |
| Met + Glim | Hypoglycaemic Episodes at Week 104 | Major | 0 episodes |
| Met + Glim | Hypoglycaemic Episodes at Week 104 | All | 524 episodes |
Secondary
Hypoglycaemic Episodes at Week 26
Total number of hypoglycaemic episodes occuring after baseline (week 0) until week 26 (end of randomisation). 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: weeks 0-26
Population: Safety analysis set is all randomised subjects who were exposed to at least one dose of study product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lira 0.6 + Met | Hypoglycaemic Episodes at Week 26 | Major | 0 episodes |
| Lira 0.6 + Met | Hypoglycaemic Episodes at Week 26 | Symptoms only | 17 episodes |
| Lira 0.6 + Met | Hypoglycaemic Episodes at Week 26 | Minor | 15 episodes |
| Lira 1.2 + Met | Hypoglycaemic Episodes at Week 26 | Major | 0 episodes |
| Lira 1.2 + Met | Hypoglycaemic Episodes at Week 26 | Minor | 3 episodes |
| Lira 1.2 + Met | Hypoglycaemic Episodes at Week 26 | Symptoms only | 7 episodes |
| Lira 1.8 + Met | Hypoglycaemic Episodes at Week 26 | Minor | 9 episodes |
| Lira 1.8 + Met | Hypoglycaemic Episodes at Week 26 | Major | 0 episodes |
| Lira 1.8 + Met | Hypoglycaemic Episodes at Week 26 | Symptoms only | 22 episodes |
| Met Mono | Hypoglycaemic Episodes at Week 26 | Minor | 6 episodes |
| Met Mono | Hypoglycaemic Episodes at Week 26 | Major | 0 episodes |
| Met Mono | Hypoglycaemic Episodes at Week 26 | Symptoms only | 10 episodes |
| Met + Glim | Hypoglycaemic Episodes at Week 26 | Major | 0 episodes |
| Met + Glim | Hypoglycaemic Episodes at Week 26 | Minor | 136 episodes |
| Met + Glim | Hypoglycaemic Episodes at Week 26 | Symptoms only | 175 episodes |