Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Asia. The trial is designed to compare the effect on glycaemic control of liraglutide or glimepiride added to metformin in subjects with type 2 diabetes
Interventions
DRUGliraglutide
0.6 mg/day, s.c. (under the skin) injection
DRUGplacebo
Glimepiride placebo, capsules
DRUGglimepiride
Capsules, 4.0 mg/day
DRUGmetformin
Tablets, 1.5-2.0 g/day
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 * Subjects diagnosed with type 2 diabetes and treated with one or more oral antidiabetic drugs (OADs) for the last 3 months * HbA1c: 7.0-11.0% (both incl.) for subjects on OAD alone * HbA1c: 7.0-10.0 % (both incl.) for subjects on OAD combination therapy * BMI less than 45.0 kg/m\^2
Exclusion criteria
* Treatment with insulin within the last 3 months prior to the trial * Impaired liver or/and renal function * Significant cardiovascular disease over the last 6 months * Known retinopathy or maculopathy * Recurrent major hypoglycaemia or hypoglycaemic unawareness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycosylated Haemoglobin A1c (HbA1c) | week 0, week 16 | Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 16 weeks (end of treatment). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Self-measured Fasting Plasma Glucose | week 0, week 16 | Change in self-measured fasting plasma glucose from baseline (week 0) to 16 weeks (end of treatment). Self-measurement of plasma glucose was performed using a glucose meter and subjects were instructed to record self-measured plasma glucose values into a diary. |
| 7-point Self-measured Plasma Glucose Profiles | week 0, 8, 12 and 16 | Summary of 7-Point Profiles of Self-Measured Plasma Glucose by Treatment, Week and Time. The 7 time points for self-measurements for all treatment groups were: Before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime, measured over 16 weeks of treatment (at week 0, 8, 12 and 16). |
| Change in Beta-cell Function | week 0, week 16 | 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 Body Weight | week 0, week 16 | Change in body weight from baseline (week 0) to 16 weeks (end of treatment) |
| Change in Fasting Lipid Profile, APO-B | week 0, week 16 | Change in fasting lipid profiles based on apolipoprotein B (Apo-B) from baseline (week 0) to 16 weeks (end of treatment). |
| Hypoglycaemic Episodes | weeks 0-16 | Total number of hypoglycaemic episodes over 16 weeks of treatment occurring from baseline (week 0) to end of treatment (week 16). 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 Fasting Lipid Profile | week 0, week 16 | Change in fasting lipid profiles from baseline (week 0) to 16 weeks (end of treatment). Fasting lipid profiles is based on: * Total Cholesterol (TC) * Low-density Lipoprotein-cholesterol (LDL-C) * Very Low-density Lipoprotein-cholesterol (VLDL-C) * High-density Lipoprotein-cholesterol (HDL-C) * Triglyceride (TG) * Free Fatty Acid (FFA) |
Countries
China, India, South Korea
Participant flow
Recruitment details
A total of 51 centres in three countries: China (17), India (24) and South Korea (10)
Pre-assignment details
A metformin run-in period of 3 weeks followed by a metformin maintenance period of 3 weeks before randomisation with dose levels increased to 2000 mg/day. Subjects already on metformin therapy at enrolment could go through a modified titration period or advance directly to the metformin maintenance period at the discretion of the investigator.
Participants by arm
| Arm | Count |
|---|---|
| Lira 0.6 + Met Liraglutide 0.6 mg once daily + metformin 1.5-2.0 g daily + glimepiride placebo | 231 |
| Lira 1.2 + Met Liraglutide 1.2 mg once daily + metformin 1.5-2.0 g daily + glimepiride placebo | 233 |
| Lira 1.8 + Met Liraglutide 1.8 mg once daily + metformin 1.5-2.0 g daily + glimepiride placebo | 234 |
| Glim + Met Glimepiride 4.0 mg + metformin 1.5-2.0 g daily + liraglutide placebo | 231 |
| Total | 929 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 22 | 30 | 3 |
| Overall Study | Did not meet trial criteria | 0 | 1 | 1 | 1 |
| Overall Study | hCG positive (not pregnant) | 0 | 0 | 1 | 0 |
| Overall Study | Hypoglycaemia | 0 | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 3 | 3 | 2 | 2 |
| Overall Study | Lack of trial product | 3 | 3 | 2 | 0 |
| Overall Study | Late syphilis, latent | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 | 3 | 4 |
| Overall Study | Protocol Violation | 2 | 5 | 3 | 1 |
| Overall Study | Taken inhibition medication eg Prandin | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 9 | 10 | 16 | 3 |
| Overall Study | Withdrawal criteria | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Lira 1.2 + Met | Lira 1.8 + Met | Lira 0.6 + Met | Glim + Met | Total |
|---|---|---|---|---|---|
| Age, Continuous | 53.5 years STANDARD_DEVIATION 9.6 | 52.7 years STANDARD_DEVIATION 9.1 | 53.5 years STANDARD_DEVIATION 9.5 | 53.6 years STANDARD_DEVIATION 9.7 | 53.3 years STANDARD_DEVIATION 9.5 |
| BMI | 25.4 kg/m2 STANDARD_DEVIATION 3.7 | 25.8 kg/m2 STANDARD_DEVIATION 3.8 | 25.9 kg/m2 STANDARD_DEVIATION 4.2 | 25.3 kg/m2 STANDARD_DEVIATION 3.7 | 25.6 kg/m2 STANDARD_DEVIATION 3.8 |
| Duration of diabetes | 7.5 years STANDARD_DEVIATION 5.3 | 7.2 years STANDARD_DEVIATION 5.2 | 7.4 years STANDARD_DEVIATION 5.4 | 7.8 years STANDARD_DEVIATION 6.1 | 7.5 years STANDARD_DEVIATION 5.5 |
| Height | 1.63 m STANDARD_DEVIATION 0.09 | 1.62 m STANDARD_DEVIATION 0.08 | 1.63 m STANDARD_DEVIATION 0.09 | 1.64 m STANDARD_DEVIATION 0.09 | 1.63 m STANDARD_DEVIATION 0.09 |
| Previous OAD treatment Combination therapy | 159 participants | 159 participants | 159 participants | 163 participants | 640 participants |
| Previous OAD treatment Mono-therapy | 74 participants | 75 participants | 72 participants | 68 participants | 289 participants |
| Sex: Female, Male Female | 105 Participants | 108 Participants | 106 Participants | 96 Participants | 415 Participants |
| Sex: Female, Male Male | 128 Participants | 126 Participants | 125 Participants | 135 Participants | 514 Participants |
| Weight | 67.4 kg STANDARD_DEVIATION 11.3 | 68.2 kg STANDARD_DEVIATION 11.9 | 68.6 kg STANDARD_DEVIATION 11.6 | 68.2 kg STANDARD_DEVIATION 11.9 | 68.1 kg STANDARD_DEVIATION 11.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 67 / 231 | 98 / 233 | 113 / 233 | 30 / 231 |
| serious Total, serious adverse events | 4 / 231 | 8 / 233 | 4 / 233 | 4 / 231 |
Outcome results
Primary
Change in Glycosylated Haemoglobin A1c (HbA1c)
Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 16 weeks (end of treatment).
Time frame: week 0, week 16
Population: The Full Analysis Set (FAS) 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 (MEAN) | Dispersion |
|---|---|---|---|
| Lira 0.6 + Met | Change in Glycosylated Haemoglobin A1c (HbA1c) | -1.0 percentage point of total HbA1c | Standard Deviation 1.04 |
| Lira 1.2 + Met | Change in Glycosylated Haemoglobin A1c (HbA1c) | -1.3 percentage point of total HbA1c | Standard Deviation 1.09 |
| Lira 1.8 + Met | Change in Glycosylated Haemoglobin A1c (HbA1c) | -1.4 percentage point of total HbA1c | Standard Deviation 1.23 |
| Glim + Met | Change in Glycosylated Haemoglobin A1c (HbA1c) | -1.3 percentage point of total HbA1c | Standard Deviation 0.98 |
Comparison: Based on standard normal theory, the sample size needed in order to be able to show that lira + met is non-inferior to glim + met when using a 1:1 randomisation and a non-inferiority criteria of 0.4% with a power of at least 85%, is tabulated below using different SD of HbA1c.~Assuming a drop out rate of 25%, the total number of subjects to be randomised is 896 (224 for each dose of the liraglutide + metformin group and 224 subjects in metformin+glimepiride treatment group) with a SD of 1.2%.p-value: <0.000195% CI: [-0.23, 0.11]ANCOVA
Comparison: Based on standard normal theory, the sample size needed in order to be able to show that lira + met is non-inferior to glim + met when using a 1:1 randomisation and a non-inferiority criteria of 0.4% with a power of at least 85%, is tabulated below using different SD of HbA1c.~Assuming a drop out rate of 25%, the total number of subjects to be randomised is 896 (224 for each dose of the liraglutide + metformin group and 224 subjects in metformin+glimepiride treatment group) with a SD of 1.2%.p-value: <0.000195% CI: [-0.14, 0.2]ANCOVA
Comparison: Based on standard normal theory, the sample size needed in order to be able to show that lira + met is non-inferior to glim + met when using a 1:1 randomisation and a non-inferiority criteria of 0.4% with a power of at least 85%, is tabulated below using different SD of HbA1c.~Assuming a drop out rate of 25%, the total number of subjects to be randomised is 896 (224 for each dose of the liraglutide + metformin group and 224 subjects in metformin+glimepiride treatment group) with a SD of 1.2%.p-value: 0.042195% CI: [0.08, 0.42]ANCOVA
Secondary
7-point Self-measured Plasma Glucose Profiles
Summary of 7-Point Profiles of Self-Measured Plasma Glucose by Treatment, Week and Time. The 7 time points for self-measurements for all treatment groups were: Before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime, measured over 16 weeks of treatment (at week 0, 8, 12 and 16).
Time frame: week 0, 8, 12 and 16
Population: The Full Analysis Set (FAS) 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 | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - Before breakfast | 168.2 mg/dl | Standard Deviation 43.5 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - 90 minutes after dinner | 195.0 mg/dl | Standard Deviation 52.2 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - 90 minutes after breakfast | 197.5 mg/dl | Standard Deviation 54.2 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - Before dinner | 194.8 mg/dl | Standard Deviation 63 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - Bedtime | 168.2 mg/dl | Standard Deviation 52.1 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - Before lunch | 141.8 mg/dl | Standard Deviation 48.3 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - 90 minutes after lunch | 183.7 mg/dl | Standard Deviation 50 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - Before breakfast | 137.8 mg/dl | Standard Deviation 33.6 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - 90 minutes after dinner | 197.2 mg/dl | Standard Deviation 51.8 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - Before dinner | 156.4 mg/dl | Standard Deviation 44.8 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - 90 minutes after dinner | 239.6 mg/dl | Standard Deviation 65.3 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - Before dinner | 151.5 mg/dl | Standard Deviation 38.5 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - Bedtime | 205.7 mg/dl | Standard Deviation 69.6 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - Bedtime | 166.4 mg/dl | Standard Deviation 50.6 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - Before breakfast | 137.0 mg/dl | Standard Deviation 31.2 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - Before lunch | 178.5 mg/dl | Standard Deviation 62.7 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - 90 minutes after lunch | 185.8 mg/dl | Standard Deviation 44.4 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - 90 minutes after breakfast | 198.5 mg/dl | Standard Deviation 55.8 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - Before lunch | 144.8 mg/dl | Standard Deviation 45.2 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - Before lunch | 140.5 mg/dl | Standard Deviation 41.3 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - 90 minutes after lunch | 187.2 mg/dl | Standard Deviation 48.7 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - Before dinner | 159.1 mg/dl | Standard Deviation 47.5 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - 90 minutes after lunch | 234.2 mg/dl | Standard Deviation 68.7 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - 90 minutes after breakfast | 195.6 mg/dl | Standard Deviation 57.1 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - 90 minutes after dinner | 193.7 mg/dl | Standard Deviation 53.2 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - Bedtime | 169.1 mg/dl | Standard Deviation 51.5 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - 90 minutes after breakfast | 245.9 mg/dl | Standard Deviation 71.6 |
| Lira 0.6 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - Before breakfast | 137.3 mg/dl | Standard Deviation 31.2 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - 90 minutes after dinner | 183.3 mg/dl | Standard Deviation 46.2 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - Before breakfast | 130.2 mg/dl | Standard Deviation 25 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - Before breakfast | 130.4 mg/dl | Standard Deviation 28 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - Bedtime | 158.9 mg/dl | Standard Deviation 45.3 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - 90 minutes after breakfast | 188.7 mg/dl | Standard Deviation 51.6 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - 90 minutes after breakfast | 185.7 mg/dl | Standard Deviation 49.4 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - 90 minutes after dinner | 187.1 mg/dl | Standard Deviation 49.3 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - Before dinner | 147.8 mg/dl | Standard Deviation 40.1 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - 90 minutes after breakfast | 190.1 mg/dl | Standard Deviation 50.8 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - Before lunch | 135.6 mg/dl | Standard Deviation 40.3 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - Before dinner | 184.8 mg/dl | Standard Deviation 65 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - 90 minutes after dinner | 185.7 mg/dl | Standard Deviation 47.1 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - Before lunch | 180.5 mg/dl | Standard Deviation 63.5 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - 90 minutes after lunch | 174.7 mg/dl | Standard Deviation 46.2 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - Before lunch | 137.0 mg/dl | Standard Deviation 40.3 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - 90 minutes after lunch | 232.3 mg/dl | Standard Deviation 67 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - Before lunch | 136.5 mg/dl | Standard Deviation 41.8 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - Before dinner | 143.4 mg/dl | Standard Deviation 36.1 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - 90 minutes after breakfast | 248.0 mg/dl | Standard Deviation 70 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - Before dinner | 148.4 mg/dl | Standard Deviation 39.8 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - Bedtime | 159.8 mg/dl | Standard Deviation 44.7 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - 90 minutes after dinner | 239.6 mg/dl | Standard Deviation 71.3 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - Before breakfast | 167.5 mg/dl | Standard Deviation 42.5 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - Before breakfast | 132.9 mg/dl | Standard Deviation 26.4 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - Bedtime | 161.6 mg/dl | Standard Deviation 47.1 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - Bedtime | 208.1 mg/dl | Standard Deviation 67.5 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - 90 minutes after lunch | 176.9 mg/dl | Standard Deviation 49.5 |
| Lira 1.2 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - 90 minutes after lunch | 181.4 mg/dl | Standard Deviation 46.7 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - 90 minutes after lunch | 173.7 mg/dl | Standard Deviation 53.1 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - Before breakfast | 168.8 mg/dl | Standard Deviation 40.4 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - 90 minutes after breakfast | 245.4 mg/dl | Standard Deviation 63.8 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - Before lunch | 176.9 mg/dl | Standard Deviation 56.8 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - 90 minutes after lunch | 234.4 mg/dl | Standard Deviation 64.2 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - Before dinner | 190.9 mg/dl | Standard Deviation 61.7 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - 90 minutes after dinner | 244.0 mg/dl | Standard Deviation 69.8 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - Bedtime | 219.3 mg/dl | Standard Deviation 71.7 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - Before breakfast | 133.7 mg/dl | Standard Deviation 28.4 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - 90 minutes after breakfast | 178.5 mg/dl | Standard Deviation 48.2 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - Before lunch | 138.0 mg/dl | Standard Deviation 37.8 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - 90 minutes after lunch | 177.9 mg/dl | Standard Deviation 48.4 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - Before dinner | 144.2 mg/dl | Standard Deviation 40.6 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - 90 minutes after dinner | 183.3 mg/dl | Standard Deviation 53.9 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - Bedtime | 155.8 mg/dl | Standard Deviation 45.6 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - Before breakfast | 130.2 mg/dl | Standard Deviation 26.8 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - 90 minutes after breakfast | 178.6 mg/dl | Standard Deviation 51.6 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - Before lunch | 134.1 mg/dl | Standard Deviation 40.3 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - Before dinner | 144.5 mg/dl | Standard Deviation 43 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - 90 minutes after dinner | 183.5 mg/dl | Standard Deviation 51.7 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - Bedtime | 158.9 mg/dl | Standard Deviation 47 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - Before breakfast | 128.6 mg/dl | Standard Deviation 26.1 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - 90 minutes after breakfast | 177.6 mg/dl | Standard Deviation 51.6 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - Before lunch | 137.8 mg/dl | Standard Deviation 40.8 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - 90 minutes after lunch | 173.2 mg/dl | Standard Deviation 50.7 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - Before dinner | 140.9 mg/dl | Standard Deviation 38.8 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - 90 minutes after dinner | 173.2 mg/dl | Standard Deviation 48.3 |
| Lira 1.8 + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - Bedtime | 151.6 mg/dl | Standard Deviation 40.3 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - Bedtime | 163.6 mg/dl | Standard Deviation 50.5 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - 90 minutes after dinner | 190.2 mg/dl | Standard Deviation 51.7 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - Before lunch | 175.8 mg/dl | Standard Deviation 61 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - Before breakfast | 131.0 mg/dl | Standard Deviation 35.3 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - Before dinner | 143.3 mg/dl | Standard Deviation 47.8 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - 90 minutes after lunch | 184.3 mg/dl | Standard Deviation 54.2 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - Bedtime | 157.7 mg/dl | Standard Deviation 47.6 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - 90 minutes after breakfast | 195.1 mg/dl | Standard Deviation 57.4 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - Before lunch | 132.6 mg/dl | Standard Deviation 46.1 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - 90 minutes after breakfast | 201.2 mg/dl | Standard Deviation 54.4 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - 90 minutes after dinner | 192.6 mg/dl | Standard Deviation 53.8 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - Before lunch | 128.8 mg/dl | Standard Deviation 45.4 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 8 - Before breakfast | 130.1 mg/dl | Standard Deviation 31.8 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - Bedtime | 202.7 mg/dl | Standard Deviation 66.4 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - 90 minutes after breakfast | 238.5 mg/dl | Standard Deviation 62.4 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - 90 minutes after lunch | 182.2 mg/dl | Standard Deviation 51.8 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - 90 minutes after dinner | 231.6 mg/dl | Standard Deviation 60.3 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - Before dinner | 180.2 mg/dl | Standard Deviation 59.2 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - Before breakfast | 163.8 mg/dl | Standard Deviation 41.2 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - Before dinner | 144.2 mg/dl | Standard Deviation 49.2 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - 90 minutes after lunch | 185.3 mg/dl | Standard Deviation 52 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - Before lunch | 129.3 mg/dl | Standard Deviation 47.7 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 16 - Before dinner | 144.9 mg/dl | Standard Deviation 45.3 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - 90 minutes after dinner | 188.5 mg/dl | Standard Deviation 50.1 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - 90 minutes after breakfast | 200.8 mg/dl | Standard Deviation 57.9 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - Before breakfast | 128.5 mg/dl | Standard Deviation 29.7 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 0 - 90 minutes after lunch | 227.6 mg/dl | Standard Deviation 67 |
| Glim + Met | 7-point Self-measured Plasma Glucose Profiles | Week 12 - Bedtime | 159.9 mg/dl | Standard Deviation 47.6 |
Secondary
Change in Beta-cell Function
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 16
Population: The Full Analysis Set (FAS) 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 (MEAN) | Dispersion |
|---|---|---|---|
| Lira 0.6 + Met | Change in Beta-cell Function | 15.3 percentage point (%point) | Standard Deviation 94.6 |
| Lira 1.2 + Met | Change in Beta-cell Function | 17.8 percentage point (%point) | Standard Deviation 30.4 |
| Lira 1.8 + Met | Change in Beta-cell Function | 21.7 percentage point (%point) | Standard Deviation 78.5 |
| Glim + Met | Change in Beta-cell Function | 21.8 percentage point (%point) | Standard Deviation 43.1 |
Secondary
Change in Body Weight
Change in body weight from baseline (week 0) to 16 weeks (end of treatment)
Time frame: week 0, week 16
Population: The Full Analysis Set (FAS) 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 (MEAN) | Dispersion |
|---|---|---|---|
| Lira 0.6 + Met | Change in Body Weight | -1.8 kg | Standard Deviation 2.2 |
| Lira 1.2 + Met | Change in Body Weight | -2.3 kg | Standard Deviation 2.4 |
| Lira 1.8 + Met | Change in Body Weight | -2.4 kg | Standard Deviation 2.6 |
| Glim + Met | Change in Body Weight | 0.1 kg | Standard Deviation 2.2 |
Secondary
Change in Fasting Lipid Profile
Change in fasting lipid profiles from baseline (week 0) to 16 weeks (end of treatment). Fasting lipid profiles is based on: * Total Cholesterol (TC) * Low-density Lipoprotein-cholesterol (LDL-C) * Very Low-density Lipoprotein-cholesterol (VLDL-C) * High-density Lipoprotein-cholesterol (HDL-C) * Triglyceride (TG) * Free Fatty Acid (FFA)
Time frame: week 0, week 16
Population: The Full Analysis Set (FAS) 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 | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lira 0.6 + Met | Change in Fasting Lipid Profile | Change in TC (Absolute), N=221, 216, 216, 228 | 0.06 mmol/L | Standard Deviation 0.74 |
| Lira 0.6 + Met | Change in Fasting Lipid Profile | Change in LDL-C (Absolute), N=221, 216, 216, 228 | 0.06 mmol/L | Standard Deviation 0.61 |
| Lira 0.6 + Met | Change in Fasting Lipid Profile | Change in VLDL-C (Absolute), N=213, 210, 207, 220 | 0.03 mmol/L | Standard Deviation 0.35 |
| Lira 0.6 + Met | Change in Fasting Lipid Profile | Change in HDL-C (Absolute), N=217, 212, 212, 220 | -0.02 mmol/L | Standard Deviation 0.19 |
| Lira 0.6 + Met | Change in Fasting Lipid Profile | Change in TG (Absolute), N=220, 212, 213, 226 | -0.08 mmol/L | Standard Deviation 0.96 |
| Lira 0.6 + Met | Change in Fasting Lipid Profile | Change in FFA (Absolute), N=218, 214, 216, 227 | -0.03 mmol/L | Standard Deviation 0.28 |
| Lira 1.2 + Met | Change in Fasting Lipid Profile | Change in FFA (Absolute), N=218, 214, 216, 227 | -0.04 mmol/L | Standard Deviation 0.28 |
| Lira 1.2 + Met | Change in Fasting Lipid Profile | Change in HDL-C (Absolute), N=217, 212, 212, 220 | -0.05 mmol/L | Standard Deviation 0.34 |
| Lira 1.2 + Met | Change in Fasting Lipid Profile | Change in TC (Absolute), N=221, 216, 216, 228 | -0.01 mmol/L | Standard Deviation 0.77 |
| Lira 1.2 + Met | Change in Fasting Lipid Profile | Change in VLDL-C (Absolute), N=213, 210, 207, 220 | 0.05 mmol/L | Standard Deviation 0.4 |
| Lira 1.2 + Met | Change in Fasting Lipid Profile | Change in LDL-C (Absolute), N=221, 216, 216, 228 | -0.03 mmol/L | Standard Deviation 0.64 |
| Lira 1.2 + Met | Change in Fasting Lipid Profile | Change in TG (Absolute), N=220, 212, 213, 226 | -0.06 mmol/L | Standard Deviation 1.13 |
| Lira 1.8 + Met | Change in Fasting Lipid Profile | Change in LDL-C (Absolute), N=221, 216, 216, 228 | 0.00 mmol/L | Standard Deviation 0.58 |
| Lira 1.8 + Met | Change in Fasting Lipid Profile | Change in VLDL-C (Absolute), N=213, 210, 207, 220 | 0.01 mmol/L | Standard Deviation 0.35 |
| Lira 1.8 + Met | Change in Fasting Lipid Profile | Change in HDL-C (Absolute), N=217, 212, 212, 220 | -0.05 mmol/L | Standard Deviation 0.15 |
| Lira 1.8 + Met | Change in Fasting Lipid Profile | Change in FFA (Absolute), N=218, 214, 216, 227 | -0.10 mmol/L | Standard Deviation 0.28 |
| Lira 1.8 + Met | Change in Fasting Lipid Profile | Change in TG (Absolute), N=220, 212, 213, 226 | -0.22 mmol/L | Standard Deviation 1.57 |
| Lira 1.8 + Met | Change in Fasting Lipid Profile | Change in TC (Absolute), N=221, 216, 216, 228 | -0.03 mmol/L | Standard Deviation 0.73 |
| Glim + Met | Change in Fasting Lipid Profile | Change in TG (Absolute), N=220, 212, 213, 226 | -0.07 mmol/L | Standard Deviation 1.26 |
| Glim + Met | Change in Fasting Lipid Profile | Change in FFA (Absolute), N=218, 214, 216, 227 | -0.02 mmol/L | Standard Deviation 0.28 |
| Glim + Met | Change in Fasting Lipid Profile | Change in LDL-C (Absolute), N=221, 216, 216, 228 | 0.04 mmol/L | Standard Deviation 0.55 |
| Glim + Met | Change in Fasting Lipid Profile | Change in HDL-C (Absolute), N=217, 212, 212, 220 | -0.01 mmol/L | Standard Deviation 0.34 |
| Glim + Met | Change in Fasting Lipid Profile | Change in TC (Absolute), N=221, 216, 216, 228 | 0.02 mmol/L | Standard Deviation 0.73 |
| Glim + Met | Change in Fasting Lipid Profile | Change in VLDL-C (Absolute), N=213, 210, 207, 220 | 0.05 mmol/L | Standard Deviation 0.42 |
Secondary
Change in Fasting Lipid Profile, APO-B
Change in fasting lipid profiles based on apolipoprotein B (Apo-B) from baseline (week 0) to 16 weeks (end of treatment).
Time frame: week 0, week 16
Population: The Full Analysis Set (FAS) 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 (MEDIAN) | Dispersion |
|---|---|---|---|
| Lira 0.6 + Met | Change in Fasting Lipid Profile, APO-B | 0.02 g/L | Standard Deviation 0.17 |
| Lira 1.2 + Met | Change in Fasting Lipid Profile, APO-B | 0.00 g/L | Standard Deviation 0.18 |
| Lira 1.8 + Met | Change in Fasting Lipid Profile, APO-B | -0.00 g/L | Standard Deviation 0.16 |
| Glim + Met | Change in Fasting Lipid Profile, APO-B | 0.01 g/L | Standard Deviation 0.17 |
Secondary
Change in Self-measured Fasting Plasma Glucose
Change in self-measured fasting plasma glucose from baseline (week 0) to 16 weeks (end of treatment). Self-measurement of plasma glucose was performed using a glucose meter and subjects were instructed to record self-measured plasma glucose values into a diary.
Time frame: week 0, week 16
Population: The Full Analysis Set (FAS) 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 (MEAN) | Dispersion |
|---|---|---|---|
| Lira 0.6 + Met | Change in Self-measured Fasting Plasma Glucose | -1.83 mg/dL | Standard Deviation 2.66 |
| Lira 1.2 + Met | Change in Self-measured Fasting Plasma Glucose | -1.96 mg/dL | Standard Deviation 2.35 |
| Lira 1.8 + Met | Change in Self-measured Fasting Plasma Glucose | -2.28 mg/dL | Standard Deviation 2.94 |
| Glim + Met | Change in Self-measured Fasting Plasma Glucose | -2.13 mg/dL | Standard Deviation 2.25 |
Secondary
Hypoglycaemic Episodes
Total number of hypoglycaemic episodes over 16 weeks of treatment occurring from baseline (week 0) to end of treatment (week 16). 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 0-16
Population: Safety Analysis Set is all randomised subjects who have been exposed to at least one dose of study products.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lira 0.6 + Met | Hypoglycaemic Episodes | Major | 0 episodes |
| Lira 0.6 + Met | Hypoglycaemic Episodes | Symptoms only | 12 episodes |
| Lira 0.6 + Met | Hypoglycaemic Episodes | Minor | 6 episodes |
| Lira 1.2 + Met | Hypoglycaemic Episodes | Major | 0 episodes |
| Lira 1.2 + Met | Hypoglycaemic Episodes | Symptoms only | 11 episodes |
| Lira 1.2 + Met | Hypoglycaemic Episodes | Minor | 0 episodes |
| Lira 1.8 + Met | Hypoglycaemic Episodes | Minor | 5 episodes |
| Lira 1.8 + Met | Hypoglycaemic Episodes | Major | 0 episodes |
| Lira 1.8 + Met | Hypoglycaemic Episodes | Symptoms only | 9 episodes |
| Glim + Met | Hypoglycaemic Episodes | Major | 2 episodes |
| Glim + Met | Hypoglycaemic Episodes | Symptoms only | 86 episodes |
| Glim + Met | Hypoglycaemic Episodes | Minor | 80 episodes |