Metabolism and Nutrition Disorder, Obesity
Conditions
Brief summary
This trial is conducted in Africa, Asia, Europe, Oceania, North America and South America. The aim of this clinical trial is to evaluate the potential of liraglutide to induce and maintain weight loss over 56 weeks in obese subjects or overweight subjects with co-morbidities. Furthermore, the aim is to investigate the long term potential of liraglutide to delay the onset of type 2 diabetes in subjects diagnosed with pre-diabetes at baseline. Based on body mass index (BMI) and pre-diabetes status, subjects will be randomised to either 68 weeks (56 weeks of randomised treatment followed by a 12 week re-randomised treatment period) or 160 weeks of treatment (160 week treatment will only be applicable to subjects with pre-diabetes status at baseline).
Interventions
DRUGliraglutide
Subject with no pre-diabetes at screening, receiving liraglutide 3.0 mg subcutaneous (under the skin) injection once daily for 56 weeks. Subjects completing 56 weeks are re-randomised to receive liraglutide 3.0 mg for 12 weeks (until week 68).
DRUGplacebo
Subject with no pre-diabetes at screening, receiving liraglutide 3.0 mg subcutaneous (under the skin) injection once daily for 56 weeks. Subjects completing 56 weeks are re-randomised to receive liraglutide placebo for 12 weeks (until week 68).
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 * Body Mass Index (BMI) of 30.0 kg/m\^2 or above * Body Mass Index (BMI) of 27 kg/m\^2 or above in the presence of co-morbidities of treated or untreated dyslipidemia and/or hypertension * Stable body weight * Preceding failed dietary effort
Exclusion criteria
* Known type 1 or type 2 diabetes * Glycosylated haemoglobin (HbA1c) of 6.5 % or above (Screening visit 1) or FPG of 126 mg/dL (7 mmol/L) or above (Screening visit 2) or 2 hour post-challenge (OGTT) plasma glucose of 200 mg/dL (11.1 mmol/L) or above (Screening visit 2) * Screening calcitonin of 50 ng/L or above * Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC) * Personal history of non-familial medullary thyroid carcinoma * 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 of 160 mmHg or above and/or diastolic blood pressure of 100 mmHg or above)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Body Weight | Week 0, Week 56 | The observed mean change from baseline in fasting body weight (%) after 56-weeks of treatment (main treatment period). |
| Proportion of Subjects Losing at Least 5% of Baseline Fasting Body Weight. | At Week 56 | Percentage of subjects losing at least 5% of baseline fasting body weight after 56-weeks of treatment (main treatment period). |
| Proportion of Subjects Losing More Than 10% of Baseline Fasting Body Weight | At 56 weeks | Percentage of subjects losing \>10% of baseline fasting body weight after 56-weeks of treatment (main treatment period). |
| Proportion of Subjects With Onset of Type 2 Diabetes | At 160 weeks | Proportion of subjects with onset of Type 2 diabetes mellitus (T2DM) at week 160 (main + extension treatment period) among subjects with pre-diabetes at baseline - evaluated as time to onset of T2DM. Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Fasting Body Weight (Subjects With Pre-diabetes at Baseline) | Week 0, week 160 | The observed mean change from baseline in fasting body weight (subjects with pre-diabetes at baseline) after 160 weeks of treatment (main + extension treatment period). Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period). |
| Proportion of Subjects Losing at Least 5% and Proportion of Subjects Losing More Than 10% of Baseline Fasting Body Weight (Subjects With Pre-diabetes at Baseline) | At 160 weeks | Percentage of subjects losing \>=5% and percentage of subjects losing \>10% of baseline fasting body weight (pre-diabetic subjects at baseline) after 160-weeks of treatment (main + extension treatment period). Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period). |
| Change From Baseline in Waist Circumference (cm) | Week 0, Week 56 | The observed mean change from baseline in waist circumference (cm) after 56-weeks of treatment (main treatment period). |
| Change From Baseline in Fasting Body Weight (%) (Re-randomised Subjects With No Pre-diabetes) | Week 0, Week 68 | The observed mean change from baseline in fasting body weight (%) in re-randomised subjects (with no pre-diabetes at baseline) after 68 weeks of treatment (main + re-randomised treatment period). |
| Change From Week 56 in Fasting Body Weight (%) (Re-randomised Subjects With No Pre-diabetes) | Week 56, Week 68 | The observed mean change in fasting body weight (%) from week 56 to week 68 in re-randomised subjects (with no pre-diabetes at baseline) after 12-weeks of treatment (re-randomised treatment period). |
| Change From Baseline in Waist Circumference (Subjects With Pre-diabetes at Baseline) | Week 0, week 160 | The observed mean change from baseline in waist circumference (subjects with pre-diabetes at baseline) after 160 weeks of treatment (main + extension treatment period). Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period). |
| Pre-diabetes Status After 56 Weeks of Treatment | Week 0, Week 56 | Observed percentage of subjects with pre-diabetes status after 56 weeks of treatment (main treatment period). |
| Pre-diabetes Status in Subject With Pre-diabetes at Baseline After 160 Weeks of Treatment | Week 0, week 160 | Observed percentage of subjects (subjects with pre-diabetes at baseline) with pre-diabetes status after 160 weeks of treatment (main + extension treatment period). Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period). |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Denmark, Finland, France, Germany, Hong Kong, Hungary, India, Ireland, Israel, Italy, Mexico, Netherlands, Norway, Poland, Russia, Serbia, Serbia and Montenegro, South Africa, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
The trial was conducted at 191 sites in 27 countries: Australia:4,Austria:3,Belgium:2, Brazil:5,Canada:11, Denmark:3,Finland:3, France:5, Germany:8,Hong Kong:1, Hungary:2, India:8, Ireland:1,Israel:7, Italy:7, Mexico:4, Netherlands:5, Norway:3, Poland:5, Russian:7, Serbia:2, South Africa:3, Spain:6, Switzerland:5,Turkey:4, UK:8, US:69.
Pre-assignment details
Subjects were stratified based on pre-diabetes status and BMI at screening. The Main Period table, below, reflects the stratification that should have occurred at baseline. The Re-randomized Period and Main + Extension Period tables reflect the actual distribution of subjects, factoring in an incorrect stratification of 43 subjects at screening.
Participants by arm
| Arm | Count |
|---|---|
| Liraglutide 3.0 mg, no Pre-diabetes Arm 1 (Arm 1A + Arm 1B): Subjects with no pre-diabetes at screening received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks followed by a re-randomisation (1:1 into liraglutide 3.0 mg or liraglutide placebo) period of 12 weeks (weeks 56-68) and then an off-drug follow-up period of 2 weeks. The total duration of this treatment arm from randomisation to follow-up was 70 weeks. | 959 |
| Liraglutide Placebo, no Pre-diabetes Arm 2: Subjects with no pre-diabetes at screening received liraglutide placebo once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks and then continued with liraglutide placebo for additional 12 weeks (weeks 56-68), followed by a 2 weeks off-drug follow-up period. The total duration of this treatment arm from randomisation to follow-up was 70 weeks. | 487 |
| Liraglutide 3.0 mg, Pre-diabetes Arm 3: Subjects with pre-diabetes at screening received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for initial 56 weeks then continued treatment till 160 weeks, followed by an off-drug, observational follow-up period of 12 weeks. The total duration of this treatment arm from randomisation to follow-up was 172 weeks. | 1,528 |
| Liraglutide Placebo, Pre-diabetes Arm 4: Subjects with pre-diabetes at screening received liraglutide placebo once daily (OD) subcutaneously (s.c. injection, under the skin) for initial 56 weeks then continued treatment till 160 weeks, followed by an off-drug, observational follow-up period of 12 weeks. The total duration of this treatment arm from randomisation to follow-up was 172 weeks. | 757 |
| Total | 3,731 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Main + Extension Period: Week 0-172 | Adverse Event | 0 | 0 | 0 | 0 | 191 | 43 |
| Main + Extension Period: Week 0-172 | Lack of Efficacy | 0 | 0 | 0 | 0 | 29 | 36 |
| Main + Extension Period: Week 0-172 | Missing reason | 0 | 0 | 0 | 0 | 1 | 0 |
| Main + Extension Period: Week 0-172 | Protocol Violation | 0 | 0 | 0 | 0 | 76 | 36 |
| Main + Extension Period: Week 0-172 | Unclassified | 0 | 0 | 0 | 0 | 61 | 51 |
| Main + Extension Period: Week 0-172 | Withdrawal criteria | 0 | 0 | 0 | 0 | 364 | 256 |
| Main Period: Week 0 to Week 56 | Adverse Event | 86 | 0 | 0 | 16 | 152 | 29 |
| Main Period: Week 0 to Week 56 | Lack of Efficacy | 11 | 0 | 0 | 14 | 12 | 22 |
| Main Period: Week 0 to Week 56 | Protocol Violation | 25 | 0 | 0 | 18 | 40 | 20 |
| Main Period: Week 0 to Week 56 | Unclassified | 36 | 0 | 0 | 29 | 42 | 34 |
| Main Period: Week 0 to Week 56 | Withdrawal criteria | 122 | 0 | 0 | 114 | 172 | 147 |
| Re-randomised Period: Week 56 to Week 68 | Adverse Event | 0 | 1 | 1 | 2 | 0 | 0 |
| Re-randomised Period: Week 56 to Week 68 | Lack of Efficacy | 0 | 0 | 0 | 1 | 0 | 0 |
| Re-randomised Period: Week 56 to Week 68 | Protocol Violation | 0 | 1 | 0 | 3 | 0 | 0 |
| Re-randomised Period: Week 56 to Week 68 | Unclassified | 0 | 1 | 2 | 2 | 0 | 0 |
| Re-randomised Period: Week 56 to Week 68 | Withdrawal criteria | 0 | 6 | 4 | 7 | 0 | 0 |
Baseline characteristics
| Characteristic | Liraglutide 3.0 mg, no Pre-diabetes | Liraglutide Placebo, no Pre-diabetes | Liraglutide 3.0 mg, Pre-diabetes | Liraglutide Placebo, Pre-diabetes | Total |
|---|---|---|---|---|---|
| Age, Continuous | 41.6 years STANDARD_DEVIATION 11.7 | 41.5 years STANDARD_DEVIATION 11.5 | 47.4 years STANDARD_DEVIATION 11.8 | 47.2 years STANDARD_DEVIATION 11.8 | 45.1 years STANDARD_DEVIATION 12 |
| Body Mass Index (BMI) | 37.5 kg/m^2 STANDARD_DEVIATION 6.2 | 37.4 kg/m^2 STANDARD_DEVIATION 6.2 | 38.8 kg/m^2 STANDARD_DEVIATION 6.4 | 39.0 kg/m^2 STANDARD_DEVIATION 6.3 | 38.3 kg/m^2 STANDARD_DEVIATION 6.4 |
| Fasting Body Weight | 104.0 kg STANDARD_DEVIATION 20.1 | 103.6 kg STANDARD_DEVIATION 21.2 | 107.6 kg STANDARD_DEVIATION 21.8 | 107.9 kg STANDARD_DEVIATION 21.8 | 106.2 kg STANDARD_DEVIATION 21.4 |
| Fasting Plasma Glucose (FPG) | 5.0 mmol/L STANDARD_DEVIATION 0.4 | 5.1 mmol/L STANDARD_DEVIATION 0.5 | 5.5 mmol/L STANDARD_DEVIATION 0.6 | 5.5 mmol/L STANDARD_DEVIATION 0.5 | 5.3 mmol/L STANDARD_DEVIATION 0.6 |
| Glycosylated Haemoglobin (HbA1c) | 5.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.3 | 5.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.3 | 5.8 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.3 | 5.7 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.3 | 5.6 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.4 |
| Sex: Female, Male Female | 801 Participants | 390 Participants | 1156 Participants | 581 Participants | 2928 Participants |
| Sex: Female, Male Male | 158 Participants | 97 Participants | 372 Participants | 176 Participants | 803 Participants |
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 | 1,342 / 1,524 | 586 / 755 | 843 / 957 | 345 / 487 |
| serious Total, serious adverse events | 230 / 1,524 | 96 / 755 | 59 / 957 | 19 / 487 |
Outcome results
Primary
Change From Baseline in Fasting Body Weight
The observed mean change from baseline in fasting body weight (%) after 56-weeks of treatment (main treatment period).
Time frame: Week 0, Week 56
Population: The full analysis set (FAS) included all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and who provided at least one post-baseline efficacy value. Missing data were imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg (56-Week) | Change From Baseline in Fasting Body Weight | -7.98 percent change | Standard Deviation 6.67 |
| Liraglutide Placebo (56-Week) | Change From Baseline in Fasting Body Weight | -2.62 percent change | Standard Deviation 5.74 |
Comparison: Null-hypothesis: no treatment difference between treatment arms, i.e. liraglutide 3.0 mg and liraglutide placebo. Liraglutide 3.0 mg was considered superior to placebo in inducing and maintaining weight loss, if the estimated treatment effect (liraglutide 3.0 mg - liraglutide placebo) was statistically significantly smaller than zero.p-value: <0.000195% CI: [-5.82, -4.95]ANCOVA
Primary
Proportion of Subjects Losing at Least 5% of Baseline Fasting Body Weight.
Percentage of subjects losing at least 5% of baseline fasting body weight after 56-weeks of treatment (main treatment period).
Time frame: At Week 56
Population: The FAS included all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and who provided at least one post-baseline efficacy value. Missing data were imputed using LOCF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liraglutide 3.0 mg (56-Week) | Proportion of Subjects Losing at Least 5% of Baseline Fasting Body Weight. | 63.2 percentage of subjects |
| Liraglutide Placebo (56-Week) | Proportion of Subjects Losing at Least 5% of Baseline Fasting Body Weight. | 27.1 percentage of subjects |
Comparison: Null-hypothesis: no treatment difference between treatment arms, i.e. liraglutide 3.0 mg and liraglutide placebo. Liraglutide 3.0 mg was considered superior to placebo in inducing and maintaining weight loss as assessed by the proportion of subjects losing ≥5% of their fasting baseline weight, if the estimated odds ratio (liraglutide 3.0 mg/liraglutide placebo) was statistically significantly greater than one.p-value: <0.000195% CI: [4.12, 5.6]Regression, Logistic
Primary
Proportion of Subjects Losing More Than 10% of Baseline Fasting Body Weight
Percentage of subjects losing \>10% of baseline fasting body weight after 56-weeks of treatment (main treatment period).
Time frame: At 56 weeks
Population: The FAS) included all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and who provided at least one post-baseline efficacy value. Missing data were imputed using LOCF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liraglutide 3.0 mg (56-Week) | Proportion of Subjects Losing More Than 10% of Baseline Fasting Body Weight | 33.1 percentage of subjects |
| Liraglutide Placebo (56-Week) | Proportion of Subjects Losing More Than 10% of Baseline Fasting Body Weight | 10.6 percentage of subjects |
Comparison: Null-hypothesis: no treatment difference between treatment arms, i.e. liraglutide 3.0 mg and liraglutide placebo. Liraglutide 3.0 mg was considered superior to placebo in inducing and maintaining weight loss as assessed by the proportion of subjects losing \>10% of their fasting baseline weight, if the estimated odds ratio (liraglutide 3.0 mg/liraglutide placebo) was statistically significantly greater than one.p-value: <0.000195% CI: [3.54, 5.32]Regression, Logistic
Primary
Proportion of Subjects With Onset of Type 2 Diabetes
Proportion of subjects with onset of Type 2 diabetes mellitus (T2DM) at week 160 (main + extension treatment period) among subjects with pre-diabetes at baseline - evaluated as time to onset of T2DM. Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period).
Time frame: At 160 weeks
Population: Subjects included in the FAS, who were stratified to 160-weeks of treatment; all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and with at least one post-baseline efficacy measurement, who were stratified to 160-weeks of treatment. Missing data were imputed using LOCF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liraglutide 3.0 mg (56-Week) | Proportion of Subjects With Onset of Type 2 Diabetes | 26 Subject |
| Liraglutide Placebo (56-Week) | Proportion of Subjects With Onset of Type 2 Diabetes | 46 Subject |
Comparison: If the estimated time-to-event ratio (liraglutide 3.0 mg/ placebo), as assessed by the survival endpoint describing the time until onset of T2DM ('diabetes-free time'), is statistically significantly \>1, then liraglutide 3.0 mg was to be considered superior to placebo in delaying the onset of T2DM in subjects with pre-diabetes at baseline. Weibull model was used; included treatment, sex and BMI stratification factor as fixed factors and baseline FPG as a covariate.p-value: <0.000195% CI: [1.856, 3.872]Weibull analysis
Secondary
Change From Baseline in Fasting Body Weight (%) (Re-randomised Subjects With No Pre-diabetes)
The observed mean change from baseline in fasting body weight (%) in re-randomised subjects (with no pre-diabetes at baseline) after 68 weeks of treatment (main + re-randomised treatment period).
Time frame: Week 0, Week 68
Population: The FAS included all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and who provided at least one post-baseline efficacy value. Missing data were imputed using LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg (56-Week) | Change From Baseline in Fasting Body Weight (%) (Re-randomised Subjects With No Pre-diabetes) | -8.44 percent change | Standard Deviation 7.23 |
| Liraglutide Placebo (56-Week) | Change From Baseline in Fasting Body Weight (%) (Re-randomised Subjects With No Pre-diabetes) | -6.77 percent change | Standard Deviation 7.67 |
| Liraglutide Placebo, no Pre-diabetes | Change From Baseline in Fasting Body Weight (%) (Re-randomised Subjects With No Pre-diabetes) | -3.11 percent change | Standard Deviation 7.52 |
Secondary
Change From Baseline in Waist Circumference (cm)
The observed mean change from baseline in waist circumference (cm) after 56-weeks of treatment (main treatment period).
Time frame: Week 0, Week 56
Population: The FAS included all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and who provided at least one post-baseline efficacy value. Missing data were imputed using LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg (56-Week) | Change From Baseline in Waist Circumference (cm) | -8.19 cm | Standard Deviation 7.31 |
| Liraglutide Placebo (56-Week) | Change From Baseline in Waist Circumference (cm) | -3.94 cm | Standard Deviation 6.58 |
Secondary
Change From Baseline in Waist Circumference (Subjects With Pre-diabetes at Baseline)
The observed mean change from baseline in waist circumference (subjects with pre-diabetes at baseline) after 160 weeks of treatment (main + extension treatment period). Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period).
Time frame: Week 0, week 160
Population: Subjects included in the FAS, who were stratified to 160-weeks of treatment; all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and with at least one post-baseline efficacy measurement, who were stratified to 160-weeks of treatment. Missing data were imputed using LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg (56-Week) | Change From Baseline in Waist Circumference (Subjects With Pre-diabetes at Baseline) | -6.87 cm | Standard Deviation 8.28 |
| Liraglutide Placebo (56-Week) | Change From Baseline in Waist Circumference (Subjects With Pre-diabetes at Baseline) | -3.37 cm | Standard Deviation 7.47 |
Secondary
Change From Week 56 in Fasting Body Weight (%) (Re-randomised Subjects With No Pre-diabetes)
The observed mean change in fasting body weight (%) from week 56 to week 68 in re-randomised subjects (with no pre-diabetes at baseline) after 12-weeks of treatment (re-randomised treatment period).
Time frame: Week 56, Week 68
Population: The FAS included all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and who provided at least one post-baseline efficacy value. Missing data were imputed using LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg (56-Week) | Change From Week 56 in Fasting Body Weight (%) (Re-randomised Subjects With No Pre-diabetes) | 0.69 percent change | Standard Deviation 2.58 |
| Liraglutide Placebo (56-Week) | Change From Week 56 in Fasting Body Weight (%) (Re-randomised Subjects With No Pre-diabetes) | 2.91 percent change | Standard Deviation 3.01 |
| Liraglutide Placebo, no Pre-diabetes | Change From Week 56 in Fasting Body Weight (%) (Re-randomised Subjects With No Pre-diabetes) | 0.28 percent change | Standard Deviation 2.39 |
Secondary
Mean Change From Baseline in Fasting Body Weight (Subjects With Pre-diabetes at Baseline)
The observed mean change from baseline in fasting body weight (subjects with pre-diabetes at baseline) after 160 weeks of treatment (main + extension treatment period). Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period).
Time frame: Week 0, week 160
Population: Subjects included in the FAS, who were stratified to 160-weeks of treatment; all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and with at least one post-baseline efficacy measurement, who were stratified to 160-weeks of treatment. Missing data were imputed using LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide 3.0 mg (56-Week) | Mean Change From Baseline in Fasting Body Weight (Subjects With Pre-diabetes at Baseline) | -6.14 percent change | Standard Deviation 7.34 |
| Liraglutide Placebo (56-Week) | Mean Change From Baseline in Fasting Body Weight (Subjects With Pre-diabetes at Baseline) | -1.89 percent change | Standard Deviation 6.27 |
Secondary
Pre-diabetes Status After 56 Weeks of Treatment
Observed percentage of subjects with pre-diabetes status after 56 weeks of treatment (main treatment period).
Time frame: Week 0, Week 56
Population: The FAS included all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and who provided at least one post-baseline efficacy value. Missing data were imputed using LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide 3.0 mg (56-Week) | Pre-diabetes Status After 56 Weeks of Treatment | With Confirmed Type 2 Diabetes | 0.2 percentage of subjects |
| Liraglutide 3.0 mg (56-Week) | Pre-diabetes Status After 56 Weeks of Treatment | With No Pre-diabetes | 78.3 percentage of subjects |
| Liraglutide 3.0 mg (56-Week) | Pre-diabetes Status After 56 Weeks of Treatment | With Pre-diabetes | 20.6 percentage of subjects |
| Liraglutide 3.0 mg (56-Week) | Pre-diabetes Status After 56 Weeks of Treatment | With Transient Type 2 Diabetes | 0.9 percentage of subjects |
| Liraglutide Placebo (56-Week) | Pre-diabetes Status After 56 Weeks of Treatment | With Transient Type 2 Diabetes | 1.8 percentage of subjects |
| Liraglutide Placebo (56-Week) | Pre-diabetes Status After 56 Weeks of Treatment | With Confirmed Type 2 Diabetes | 1.1 percentage of subjects |
| Liraglutide Placebo (56-Week) | Pre-diabetes Status After 56 Weeks of Treatment | With Pre-diabetes | 46.1 percentage of subjects |
| Liraglutide Placebo (56-Week) | Pre-diabetes Status After 56 Weeks of Treatment | With No Pre-diabetes | 50.9 percentage of subjects |
Secondary
Pre-diabetes Status in Subject With Pre-diabetes at Baseline After 160 Weeks of Treatment
Observed percentage of subjects (subjects with pre-diabetes at baseline) with pre-diabetes status after 160 weeks of treatment (main + extension treatment period). Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period).
Time frame: Week 0, week 160
Population: Subjects included in the FAS, who were stratified to 160-weeks of treatment; all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and with at least one post-baseline efficacy measurement, who were stratified to 160-weeks of treatment. Missing data were imputed using LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide 3.0 mg (56-Week) | Pre-diabetes Status in Subject With Pre-diabetes at Baseline After 160 Weeks of Treatment | With Transient Type 2 Diabetes | 1.1 percentage of subjects |
| Liraglutide 3.0 mg (56-Week) | Pre-diabetes Status in Subject With Pre-diabetes at Baseline After 160 Weeks of Treatment | With No Pre-diabetes | 65.9 percentage of subjects |
| Liraglutide 3.0 mg (56-Week) | Pre-diabetes Status in Subject With Pre-diabetes at Baseline After 160 Weeks of Treatment | With Pre-diabetes | 31.3 percentage of subjects |
| Liraglutide 3.0 mg (56-Week) | Pre-diabetes Status in Subject With Pre-diabetes at Baseline After 160 Weeks of Treatment | With Confirmed Type 2 Diabetes | 1.8 percentage of subjects |
| Liraglutide Placebo (56-Week) | Pre-diabetes Status in Subject With Pre-diabetes at Baseline After 160 Weeks of Treatment | With Confirmed Type 2 Diabetes | 6.2 percentage of subjects |
| Liraglutide Placebo (56-Week) | Pre-diabetes Status in Subject With Pre-diabetes at Baseline After 160 Weeks of Treatment | With Transient Type 2 Diabetes | 2.6 percentage of subjects |
| Liraglutide Placebo (56-Week) | Pre-diabetes Status in Subject With Pre-diabetes at Baseline After 160 Weeks of Treatment | With Pre-diabetes | 54.9 percentage of subjects |
| Liraglutide Placebo (56-Week) | Pre-diabetes Status in Subject With Pre-diabetes at Baseline After 160 Weeks of Treatment | With No Pre-diabetes | 36.3 percentage of subjects |
Secondary
Proportion of Subjects Losing at Least 5% and Proportion of Subjects Losing More Than 10% of Baseline Fasting Body Weight (Subjects With Pre-diabetes at Baseline)
Percentage of subjects losing \>=5% and percentage of subjects losing \>10% of baseline fasting body weight (pre-diabetic subjects at baseline) after 160-weeks of treatment (main + extension treatment period). Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period).
Time frame: At 160 weeks
Population: Subjects included in the FAS, who were stratified to 160-weeks of treatment; all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and with at least one post-baseline efficacy measurement, who were stratified to 160-weeks of treatment. Missing data were imputed using LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide 3.0 mg (56-Week) | Proportion of Subjects Losing at Least 5% and Proportion of Subjects Losing More Than 10% of Baseline Fasting Body Weight (Subjects With Pre-diabetes at Baseline) | Losing >=5% of baseline body weight | 49.6 percentage of subjects |
| Liraglutide 3.0 mg (56-Week) | Proportion of Subjects Losing at Least 5% and Proportion of Subjects Losing More Than 10% of Baseline Fasting Body Weight (Subjects With Pre-diabetes at Baseline) | Losing >10% of baseline body weight | 24.8 percentage of subjects |
| Liraglutide Placebo (56-Week) | Proportion of Subjects Losing at Least 5% and Proportion of Subjects Losing More Than 10% of Baseline Fasting Body Weight (Subjects With Pre-diabetes at Baseline) | Losing >=5% of baseline body weight | 23.7 percentage of subjects |
| Liraglutide Placebo (56-Week) | Proportion of Subjects Losing at Least 5% and Proportion of Subjects Losing More Than 10% of Baseline Fasting Body Weight (Subjects With Pre-diabetes at Baseline) | Losing >10% of baseline body weight | 9.9 percentage of subjects |