Metabolism and Nutrition Disorder, Obesity
Conditions
Brief summary
This trial is conducted in Africa, Asia, Europe and the United States of America (USA). The aim of this trial is to investigate the potential of liraglutide to induce and maintain weight loss in overweight or obese subjects with type 2 diabetes. Treatment will be added onto subject's pre-trial background diabetes treatment of either diet and exercise only or single compound oral antidiabetic drug (OAD) treatment (metformin, sulphonylurea \[SU\] or glitazone) or combination OAD treatment (metformin, sulphonylurea or glitazone). The duration of the trial will be 56 weeks followed by a 12 week observational follow-up period.
Interventions
DRUGliraglutide
Liraglutide 3.0 mg for subcutaneous (under the skin) injection once daily for 56 weeks.
DRUGplacebo
Liraglutide placebo of either 3.0 mg or 1.8 mg for subcutaneous (under the skin) injection once daily for 56 weeks.
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Informed consent obtained * Subjects diagnosed with type 2 diabetes and treated with either diet and exercise alone, metformin, sulphonylurea, glitazone as single agent therapy or a combination of the previously mentioned compounds * HbA1c 7.0-10.0% (both inclusive) * Body Mass Index (BMI) at least 27.0 kg/m\^2 * Stable body weight * Preceding failed dietary effort
Exclusion criteria
* Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors or insulin within the last 3 months * Known proliferative retinopathy or maculopathy * History of acute or chronic pancreatitis * Obesity induced by drug treatment * Use of approved weight lowering pharmacotherapy * Previous surgical treatment of obesity * History of major depressive disorder or suicide attempt * Uncontrolled hypertension (systolic blood pressure above or equal to 160 mmHg and/or diastolic blood pressure above or equal to 100 mmHg) * Screening calcitonin of 50 ng/L or above * Familial or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC) * Personal history of non-familial medullary thyroid carcinoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change (%) From Baseline in Body Weight (Fasting) | Week 0, week 56 | Weight was recorded to the nearest 0.1 kg for a subject in the fasting state with an empty bladder, without shoes and only wearing light clothing. The same calibrated scale was used throughout the trial. |
| Proportion of Subjects Losing at Least 5% of Baseline Body Weight | at 56 weeks | Weight was recorded to the nearest 0.1 kg for a subject in the fasting state with an empty bladder, without shoes and only wearing light clothing. The same calibrated scale was used throughout the trial. |
| Proportion of Subjects Losing More Than 10% of Baseline Body Weight | at 56 weeks | Weight was recorded to the nearest 0.1 kg for a subject in the fasting state with an empty bladder, without shoes and only wearing light clothing. The same calibrated scale was used throughout the trial. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Waist Circumference | Week 0, week 56 | — |
| Change (%) From Baseline in Body Weight (Fasting) | Week 0, week 68 | Weight was recorded to the nearest 0.1 kg for a subject in the fasting state with an empty bladder, without shoes and only wearing light clothing. The same calibrated scale was used throughout the trial. |
| Change (%-Points) From Baseline in HbA1c (Glycosylated Haemoglobin A1c) | Week 0, week 56 | Change in HbA1c (%-points) was calculated as the difference between the HbA1c (%) at Week 0 and Week 56. |
| Change From Week 56 to 68 in Waist Circumference | Week 56, week 68 | — |
| Incidence of Hypoglycaemic Episodes | Weeks 0-56 | Hypoglycaemic episodes were classified according to American Diabetes Association (ADA) definitions as well as to the Novo Nordisk definition of a minor hypoglycaemic event (blood glucose level below approximately 2.8 mmol/L \[50 mg/dL\] or plasma glucose level below 3.1 mmol/L \[56 mg/dL\]). |
| Change (%) From Week 56 to 68 in Body Weight (Fasting) | Week 56, week 68 | Weight was recorded to the nearest 0.1 kg for a subject in the fasting state with an empty bladder, without shoes and only wearing light clothing. The same calibrated scale was used throughout the trial. |
| Proportion of Subjects Reaching Target HbA1c Below 7% | at 56 weeks | — |
| Proportion of Subjects Reaching Target HbA1c Below or Equal to 6.5% | at 56 weeks | — |
Countries
France, Germany, India, Israel, Italy, Puerto Rico, South Africa, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
A total of 126 sites in 9 countries participated: France (7), Germany (10), Israel (5), South Africa (6), Spain (8), Sweden (5), Turkey (3), United Kingdom (15), United States (67).
Pre-assignment details
If eligible based on screened assessments, subjects were randomised to 1 of the 3 treatment arms in a 2:1:1 manner (liraglutide 3.0 mg, liraglutide 1.8 mg and placebo, respectively).
Participants by arm
| Arm | Count |
|---|---|
| Liraglutide 3.0 mg Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 3.0 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 3.0 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%. | 423 |
| Liraglutide 1.8 mg Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide, titrated from a starting dose of 0.6 mg in weekly increments of 0.6 mg to the target dose of 1.8 mg. In the 12-week follow-up period, treatment was discontinued. In addition to liraglutide 1.8 mg treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%. | 211 |
| Liraglutide Placebo Exposed subjects received 56 weeks of once-daily subcutaneous (s.c.) injections with liraglutide placebo. In the 12-week follow-up period, treatment was discontinued. In addition to placebo treatment, subjects were instructed to follow a hypocaloric diet and an exercise programme. Pre-trial treatment with metformin, glitazone or sulphonorylureas (SU) was continued throughout the trial (open-label) at unchanged dose, expect for SU that was reduced by 50%. | 212 |
| Total | 846 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Off Drug Follow-up Period (Weeks 56-68) | Adverse Event | 1 | 1 | 0 |
| Off Drug Follow-up Period (Weeks 56-68) | Lack of Efficacy | 1 | 0 | 0 |
| Off Drug Follow-up Period (Weeks 56-68) | Protocol Violation | 1 | 0 | 1 |
| Off Drug Follow-up Period (Weeks 56-68) | Unclassified | 2 | 2 | 0 |
| Off Drug Follow-up Period (Weeks 56-68) | Withdrawal criteria | 9 | 7 | 4 |
| Weeks 0-56 | Adverse Event | 39 | 18 | 7 |
| Weeks 0-56 | Lack of Efficacy | 0 | 0 | 3 |
| Weeks 0-56 | Protocol Violation | 12 | 8 | 13 |
| Weeks 0-56 | Unclassified | 16 | 7 | 12 |
| Weeks 0-56 | Withdrawal criteria | 32 | 14 | 37 |
Baseline characteristics
| Characteristic | Liraglutide 3.0 mg | Liraglutide 1.8 mg | Liraglutide Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 55.0 years STANDARD_DEVIATION 10.8 | 54.9 years STANDARD_DEVIATION 10.7 | 54.7 years STANDARD_DEVIATION 9.8 | 54.9 years STANDARD_DEVIATION 10.5 |
| Age group 18- < 40 years | 38 participants | 15 participants | 13 participants | 66 participants |
| Age group 40- < 65 years | 300 participants | 162 participants | 161 participants | 623 participants |
| Age group 65- < 75 years | 74 participants | 32 participants | 36 participants | 142 participants |
| Age group >= 75 years | 11 participants | 2 participants | 2 participants | 15 participants |
| Body Mass Index (BMI) | 37.1 kg/m^2 STANDARD_DEVIATION 6.5 | 37.0 kg/m^2 STANDARD_DEVIATION 6.9 | 37.4 kg/m^2 STANDARD_DEVIATION 7.1 | 37.1 kg/m^2 STANDARD_DEVIATION 6.8 |
| Body Mass Index (BMI) group 25.0-29.9 kg/m^2 - pre-obese | 52 participants | 34 participants | 30 participants | 116 participants |
| Body Mass Index (BMI) group 30.0-34.9 kg/m^2 - obese class I | 139 participants | 62 participants | 59 participants | 260 participants |
| Body Mass Index (BMI) group 35.0-39.9 kg/m^2 - obese class II | 108 participants | 50 participants | 60 participants | 218 participants |
| Body Mass Index (BMI) group >40.0 kg/m^2 - obese class III | 124 participants | 65 participants | 63 participants | 252 participants |
| Co-morbid dyslipidaemia Absent | 128 participants | 68 participants | 86 participants | 282 participants |
| Co-morbid dyslipidaemia Present | 295 participants | 143 participants | 126 participants | 564 participants |
| Co-morbid hypertension Absent | 130 participants | 63 participants | 67 participants | 260 participants |
| Co-morbid hypertension Present | 293 participants | 148 participants | 145 participants | 586 participants |
| Duration of diabetes | 7.54 years STANDARD_DEVIATION 5.65 | 7.43 years STANDARD_DEVIATION 5.16 | 6.71 years STANDARD_DEVIATION 5.07 | 7.30 years STANDARD_DEVIATION 5.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 46 Participants | 17 Participants | 24 Participants | 87 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 375 Participants | 194 Participants | 187 Participants | 756 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Fasting body weight | 105.7 kg STANDARD_DEVIATION 21.9 | 105.8 kg STANDARD_DEVIATION 21 | 106.5 kg STANDARD_DEVIATION 21.3 | 105.9 kg STANDARD_DEVIATION 21.5 |
| Fasting plasma glucose | 8.8 mmol/L STANDARD_DEVIATION 1.9 | 8.9 mmol/L STANDARD_DEVIATION 2 | 8.6 mmol/L STANDARD_DEVIATION 1.8 | 8.8 mmol/L STANDARD_DEVIATION 1.9 |
| HbA1c (glycosylated haemoglobin) | 7.9 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.8 | 8.0 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.8 | 7.9 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.8 | 7.9 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.8 |
| Height | 1.69 m STANDARD_DEVIATION 0.11 | 1.69 m STANDARD_DEVIATION 0.1 | 1.69 m STANDARD_DEVIATION 0.1 | 1.69 m STANDARD_DEVIATION 0.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 4 Participants | 4 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 44 Participants | 27 Participants | 27 Participants | 98 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 11 Participants | 3 Participants | 6 Participants | 20 Participants |
| Race (NIH/OMB) White | 353 Participants | 177 Participants | 175 Participants | 705 Participants |
| Sex: Female, Male Female | 203 Participants | 103 Participants | 115 Participants | 421 Participants |
| Sex: Female, Male Male | 220 Participants | 108 Participants | 97 Participants | 425 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 361 / 422 | 173 / 210 | 164 / 212 |
| serious Total, serious adverse events | 37 / 422 | 18 / 210 | 13 / 212 |
Outcome results
Primary
Change (%) From Baseline in Body Weight (Fasting)
Weight was recorded to the nearest 0.1 kg for a subject in the fasting state with an empty bladder, without shoes and only wearing light clothing. The same calibrated scale was used throughout the trial.
Time frame: Week 0, week 56
Population: Last Observation Carried Forward (LOCF) data. Full analysis set, comprising all randomised subjects who had been exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change (%) From Baseline in Body Weight (Fasting) | -5.9 percent change | Standard Deviation 5.5 |
| Liraglutide 1.8 mg | Change (%) From Baseline in Body Weight (Fasting) | -4.6 percent change | Standard Deviation 5.5 |
| Liraglutide Placebo | Change (%) From Baseline in Body Weight (Fasting) | -2.0 percent change | Standard Deviation 4.3 |
Comparison: The 3 co-primary endpoints (Outcome Measures 1, 2 and 3) were ranked (#1, 2, 3); hypotheses of no difference were tested in a hierarchical manner. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: <0.000195% CI: [-4.84, -3.11]ANCOVA
Comparison: The 3 co-primary endpoints (Outcome Measures 1, 2 and 3) were ranked (#1, 2, 3); hypotheses of no difference were tested in a hierarchical manner. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: <0.000195% CI: [-3.63, -1.62]ANCOVA
Comparison: The 3 co-primary endpoints (Outcome Measures 1, 2 and 3) were ranked (#1, 2, 3); hypotheses of no difference were tested in a hierarchical manner. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: 0.002495% CI: [-2.23, -0.48]ANCOVA
Primary
Proportion of Subjects Losing at Least 5% of Baseline Body Weight
Weight was recorded to the nearest 0.1 kg for a subject in the fasting state with an empty bladder, without shoes and only wearing light clothing. The same calibrated scale was used throughout the trial.
Time frame: at 56 weeks
Population: Last Observation Carried Forward (LOCF) data. Full analysis set, comprising all randomised subjects who had been exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide 3.0 mg | Proportion of Subjects Losing at Least 5% of Baseline Body Weight | Yes | 49.9 percentage of subjects |
| Liraglutide 3.0 mg | Proportion of Subjects Losing at Least 5% of Baseline Body Weight | No | 50.1 percentage of subjects |
| Liraglutide 1.8 mg | Proportion of Subjects Losing at Least 5% of Baseline Body Weight | Yes | 35.6 percentage of subjects |
| Liraglutide 1.8 mg | Proportion of Subjects Losing at Least 5% of Baseline Body Weight | No | 64.4 percentage of subjects |
| Liraglutide Placebo | Proportion of Subjects Losing at Least 5% of Baseline Body Weight | Yes | 13.8 percentage of subjects |
| Liraglutide Placebo | Proportion of Subjects Losing at Least 5% of Baseline Body Weight | No | 86.2 percentage of subjects |
Comparison: The 3 co-primary endpoints (Outcome Measures 1, 2 and 3) were ranked (#1, 2, 3); hypotheses of no difference were tested in a hierarchical manner. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: <0.000195% CI: [4.34, 10.68]Regression, Logistic
Comparison: The 3 co-primary endpoints (Outcome Measures 1, 2 and 3) were ranked (#1, 2, 3); hypotheses of no difference were tested in a hierarchical manner. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: <0.000195% CI: [2.24, 6.09]Regression, Logistic
Comparison: The 3 co-primary endpoints (Outcome Measures 1, 2 and 3) were ranked (#1, 2, 3); hypotheses of no difference were tested in a hierarchical manner. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: 0.000895% CI: [1.29, 2.64]Regression, Logistic
Primary
Proportion of Subjects Losing More Than 10% of Baseline Body Weight
Weight was recorded to the nearest 0.1 kg for a subject in the fasting state with an empty bladder, without shoes and only wearing light clothing. The same calibrated scale was used throughout the trial.
Time frame: at 56 weeks
Population: Last Observation Carried Forward (LOCF) data. Full analysis set, comprising all randomised subjects who had been exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide 3.0 mg | Proportion of Subjects Losing More Than 10% of Baseline Body Weight | Yes | 23.4 percentage of subjects |
| Liraglutide 3.0 mg | Proportion of Subjects Losing More Than 10% of Baseline Body Weight | No | 76.6 percentage of subjects |
| Liraglutide 1.8 mg | Proportion of Subjects Losing More Than 10% of Baseline Body Weight | Yes | 14.4 percentage of subjects |
| Liraglutide 1.8 mg | Proportion of Subjects Losing More Than 10% of Baseline Body Weight | No | 85.6 percentage of subjects |
| Liraglutide Placebo | Proportion of Subjects Losing More Than 10% of Baseline Body Weight | Yes | 4.3 percentage of subjects |
| Liraglutide Placebo | Proportion of Subjects Losing More Than 10% of Baseline Body Weight | No | 95.7 percentage of subjects |
Comparison: The 3 co-primary endpoints (Outcome Measures 1, 2 and 3) were ranked (#1, 2, 3); hypotheses of no difference were tested in a hierarchical manner. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: <0.000195% CI: [3.48, 14.48]Regression, Logistic
Comparison: The 3 co-primary endpoints (Outcome Measures 1, 2 and 3) were ranked (#1, 2, 3); hypotheses of no difference were tested in a hierarchical manner. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: 0.000895% CI: [1.75, 8.41]Regression, Logistic
Comparison: The 3 co-primary endpoints (Outcome Measures 1, 2 and 3) were ranked (#1, 2, 3); hypotheses of no difference were tested in a hierarchical manner. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: 0.009995% CI: [1.16, 2.95]Regression, Logistic
Secondary
Change (%) From Baseline in Body Weight (Fasting)
Weight was recorded to the nearest 0.1 kg for a subject in the fasting state with an empty bladder, without shoes and only wearing light clothing. The same calibrated scale was used throughout the trial.
Time frame: Week 0, week 68
Population: Full analysis set, comprising all randomised subjects who had been exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change (%) From Baseline in Body Weight (Fasting) | -4.7 percent change | Standard Deviation 5 |
| Liraglutide 1.8 mg | Change (%) From Baseline in Body Weight (Fasting) | -3.6 percent change | Standard Deviation 5.7 |
| Liraglutide Placebo | Change (%) From Baseline in Body Weight (Fasting) | -2.7 percent change | Standard Deviation 5.8 |
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: 0.000295% CI: [-3.32, -1.02]ANCOVA
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: 0.072595% CI: [-2.51, 0.11]ANCOVA
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: 0.071795% CI: [-2.02, 0.09]ANCOVA
Secondary
Change From Baseline in Waist Circumference
Time frame: Week 0, week 56
Population: Last Observation Carried Forward (LOCF) data. Full analysis set, comprising all randomised subjects who had been exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Baseline in Waist Circumference | -6.1 cm | Standard Deviation 6.5 |
| Liraglutide 1.8 mg | Change From Baseline in Waist Circumference | -4.8 cm | Standard Deviation 5.6 |
| Liraglutide Placebo | Change From Baseline in Waist Circumference | -2.7 cm | Standard Deviation 5.4 |
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: <0.000195% CI: [-4.2, -2.23]ANCOVA
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: 0.000495% CI: [-3.2, -0.92]ANCOVA
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: 0.022495% CI: [-2.16, -0.16]ANCOVA
Secondary
Change From Baseline in Waist Circumference
Time frame: Week 0, week 68
Population: Full analysis set, comprising all randomised subjects who had been exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Baseline in Waist Circumference | -5.7 cm | Standard Deviation 6.3 |
| Liraglutide 1.8 mg | Change From Baseline in Waist Circumference | -4.4 cm | Standard Deviation 6 |
| Liraglutide Placebo | Change From Baseline in Waist Circumference | -3.2 cm | Standard Deviation 6.8 |
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: <0.000195% CI: [-3.75, -1.24]ANCOVA
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: 0.045795% CI: [-2.92, -0.03]ANCOVA
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: 0.096195% CI: [-2.22, 0.18]ANCOVA
Secondary
Change (%) From Week 56 to 68 in Body Weight (Fasting)
Weight was recorded to the nearest 0.1 kg for a subject in the fasting state with an empty bladder, without shoes and only wearing light clothing. The same calibrated scale was used throughout the trial.
Time frame: Week 56, week 68
Population: Last Observation Carried Forward (LOCF) data. Full analysis set, comprising all randomised subjects who had been exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change (%) From Week 56 to 68 in Body Weight (Fasting) | 2.3 percent change | Standard Deviation 2.9 |
| Liraglutide 1.8 mg | Change (%) From Week 56 to 68 in Body Weight (Fasting) | 2.0 percent change | Standard Deviation 2.9 |
| Liraglutide Placebo | Change (%) From Week 56 to 68 in Body Weight (Fasting) | -0.1 percent change | Standard Deviation 2.2 |
Secondary
Change From Week 56 to 68 in Waist Circumference
Time frame: Week 56, week 68
Population: Last Observation Carried Forward (LOCF) data. Full analysis set, comprising all randomised subjects who had been exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change From Week 56 to 68 in Waist Circumference | 1.21 cm | Standard Deviation 3.94 |
| Liraglutide 1.8 mg | Change From Week 56 to 68 in Waist Circumference | 1.02 cm | Standard Deviation 3.55 |
| Liraglutide Placebo | Change From Week 56 to 68 in Waist Circumference | -0.22 cm | Standard Deviation 3.23 |
Secondary
Change (%-Points) From Baseline in HbA1c (Glycosylated Haemoglobin A1c)
Change in HbA1c (%-points) was calculated as the difference between the HbA1c (%) at Week 0 and Week 56.
Time frame: Week 0, week 56
Population: Last Observation Carried Forward (LOCF) data. Full analysis set, comprising all randomised subjects who had been exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg | Change (%-Points) From Baseline in HbA1c (Glycosylated Haemoglobin A1c) | -1.3 percentage point change of HbA1c | Standard Deviation 0.9 |
| Liraglutide 1.8 mg | Change (%-Points) From Baseline in HbA1c (Glycosylated Haemoglobin A1c) | -1.1 percentage point change of HbA1c | Standard Deviation 1 |
| Liraglutide Placebo | Change (%-Points) From Baseline in HbA1c (Glycosylated Haemoglobin A1c) | -0.3 percentage point change of HbA1c | Standard Deviation 0.9 |
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: <0.000195% CI: [-1.08, -0.78]ANCOVA
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: <0.000195% CI: [-0.91, -0.57]ANCOVA
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: 0.012595% CI: [-0.34, -0.04]ANCOVA
Secondary
Incidence of Hypoglycaemic Episodes
Hypoglycaemic episodes were classified according to American Diabetes Association (ADA) definitions as well as to the Novo Nordisk definition of a minor hypoglycaemic event (blood glucose level below approximately 2.8 mmol/L \[50 mg/dL\] or plasma glucose level below 3.1 mmol/L \[56 mg/dL\]).
Time frame: Weeks 0-56
Population: Safety analysis set, comprising all randomised subjects who had been exposed to at least one dose of trial product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide 3.0 mg | Incidence of Hypoglycaemic Episodes | ADA: Probable, symptomatic | 2 Episodes/100 years of patient exposure |
| Liraglutide 3.0 mg | Incidence of Hypoglycaemic Episodes | ADA: Severe | 1 Episodes/100 years of patient exposure |
| Liraglutide 3.0 mg | Incidence of Hypoglycaemic Episodes | ADA: Relative | 17 Episodes/100 years of patient exposure |
| Liraglutide 3.0 mg | Incidence of Hypoglycaemic Episodes | ADA: Unclassifiable | 14 Episodes/100 years of patient exposure |
| Liraglutide 3.0 mg | Incidence of Hypoglycaemic Episodes | Minor | 34 Episodes/100 years of patient exposure |
| Liraglutide 3.0 mg | Incidence of Hypoglycaemic Episodes | ADA: Documented, symptomatic | 87 Episodes/100 years of patient exposure |
| Liraglutide 3.0 mg | Incidence of Hypoglycaemic Episodes | ADA: Asymptomatic | 151 Episodes/100 years of patient exposure |
| Liraglutide 1.8 mg | Incidence of Hypoglycaemic Episodes | ADA: Relative | 16 Episodes/100 years of patient exposure |
| Liraglutide 1.8 mg | Incidence of Hypoglycaemic Episodes | ADA: Asymptomatic | 142 Episodes/100 years of patient exposure |
| Liraglutide 1.8 mg | Incidence of Hypoglycaemic Episodes | ADA: Documented, symptomatic | 95 Episodes/100 years of patient exposure |
| Liraglutide 1.8 mg | Incidence of Hypoglycaemic Episodes | ADA: Severe | 2 Episodes/100 years of patient exposure |
| Liraglutide 1.8 mg | Incidence of Hypoglycaemic Episodes | Minor | 46 Episodes/100 years of patient exposure |
| Liraglutide 1.8 mg | Incidence of Hypoglycaemic Episodes | ADA: Unclassifiable | 7 Episodes/100 years of patient exposure |
| Liraglutide 1.8 mg | Incidence of Hypoglycaemic Episodes | ADA: Probable, symptomatic | 2 Episodes/100 years of patient exposure |
| Liraglutide Placebo | Incidence of Hypoglycaemic Episodes | ADA: Unclassifiable | 3 Episodes/100 years of patient exposure |
| Liraglutide Placebo | Incidence of Hypoglycaemic Episodes | Minor | 13 Episodes/100 years of patient exposure |
| Liraglutide Placebo | Incidence of Hypoglycaemic Episodes | ADA: Severe | 0 Episodes/100 years of patient exposure |
| Liraglutide Placebo | Incidence of Hypoglycaemic Episodes | ADA: Documented, symptomatic | 31 Episodes/100 years of patient exposure |
| Liraglutide Placebo | Incidence of Hypoglycaemic Episodes | ADA: Asymptomatic | 46 Episodes/100 years of patient exposure |
| Liraglutide Placebo | Incidence of Hypoglycaemic Episodes | ADA: Probable, symptomatic | 1 Episodes/100 years of patient exposure |
| Liraglutide Placebo | Incidence of Hypoglycaemic Episodes | ADA: Relative | 5 Episodes/100 years of patient exposure |
Secondary
Proportion of Subjects Reaching Target HbA1c Below 7%
Time frame: at 56 weeks
Population: Last Observation Carried Forward (LOCF) data. Full analysis set, comprising all randomised subjects who had been exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide 3.0 mg | Proportion of Subjects Reaching Target HbA1c Below 7% | Yes | 69.2 percentage of subjects |
| Liraglutide 3.0 mg | Proportion of Subjects Reaching Target HbA1c Below 7% | No | 30.8 percentage of subjects |
| Liraglutide 1.8 mg | Proportion of Subjects Reaching Target HbA1c Below 7% | Yes | 66.7 percentage of subjects |
| Liraglutide 1.8 mg | Proportion of Subjects Reaching Target HbA1c Below 7% | No | 33.3 percentage of subjects |
| Liraglutide Placebo | Proportion of Subjects Reaching Target HbA1c Below 7% | Yes | 27.2 percentage of subjects |
| Liraglutide Placebo | Proportion of Subjects Reaching Target HbA1c Below 7% | No | 72.8 percentage of subjects |
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: <0.000195% CI: [5.74, 13.4]Regression, Logistic
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: <0.000195% CI: [4.76, 12.51]Regression, Logistic
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: 0.531995% CI: [0.76, 1.71]Regression, Logistic
Secondary
Proportion of Subjects Reaching Target HbA1c Below or Equal to 6.5%
Time frame: at 56 weeks
Population: Last Observation Carried Forward (LOCF) data. Full analysis set, comprising all randomised subjects who had been exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide 3.0 mg | Proportion of Subjects Reaching Target HbA1c Below or Equal to 6.5% | Yes | 56.5 percentage of subjects |
| Liraglutide 3.0 mg | Proportion of Subjects Reaching Target HbA1c Below or Equal to 6.5% | No | 43.5 percentage of subjects |
| Liraglutide 1.8 mg | Proportion of Subjects Reaching Target HbA1c Below or Equal to 6.5% | Yes | 45.6 percentage of subjects |
| Liraglutide 1.8 mg | Proportion of Subjects Reaching Target HbA1c Below or Equal to 6.5% | No | 54.4 percentage of subjects |
| Liraglutide Placebo | Proportion of Subjects Reaching Target HbA1c Below or Equal to 6.5% | Yes | 15.0 percentage of subjects |
| Liraglutide Placebo | Proportion of Subjects Reaching Target HbA1c Below or Equal to 6.5% | No | 85.0 percentage of subjects |
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: <0.000195% CI: [6.05, 15.26]Regression, Logistic
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: <0.000195% CI: [3.59, 9.97]Regression, Logistic
Comparison: Test of no difference. Fixed factors: treatment, country, sex, background treatment, baseline HbA1c stratum, background treatment/HbA1c-stratum-interaction; covariate: baseline value.p-value: 0.014295% CI: [1.1, 2.34]Regression, Logistic