Metabolism and Nutrition Disorder, Obesity
Conditions
Brief summary
This trial is conducted in North America. The aim of this clinical trial is to evaluate the potential of liraglutide to maintain long term weight loss in obese non-diabetic subjects, as well as in overweight subjects who have medical problems such as hypertension (high blood pressure) or dyslipidaemia (an abnormal amount of lipids in the blood). Trial has following trial periods: A 12-week run-in period (from week -12 to week 0) followed by a 56-week main trial period (weeks 0-56) and a 12-week follow-up period (weeks 56-68).
Interventions
DRUGliraglutide
Liraglutide 3.0 mg per day administered in a 6.0 mg/mL, 3 mL FlexPen® for subcutaneous (under the skin) injection, once daily
DRUGplacebo
Liraglutide placebo 3 mL FlexPen® for subcutaneous (under the skin) injection, once daily
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Body Mass Index (BMI) of either 30 kg/m\^2 or more or BMI of less than 30 kg/m\^2 to 27 kg/m\^2 with presence of co-morbidities * Stable body weight during the previous 3 months (less than 5 kg self-reported weight change) * Previously undergone dietary weight loss and was not able to maintain reduced weight
Exclusion criteria
* Diagnosis of type 1 or type 2 diabetes * Previous treatment with GLP-1 (glucagon-like peptide-1) receptor agonists (including liraglutide or exenatide), within the last 3 months * Visit 1 thryoid stimulating hormone (TSH) outside of the range of 0.4-6.0 mIU/L * History of chronic pancreatitis or idiopathic acute pancreatitis * Obesity induced by other endocrinologic disorders (e.g., Cushing Syndrome) * Current or history of treatment with medications that may cause significant weight gain for at least 3 months before this trial * Current participation in an organized diet reduction program (or within the last 3 months) * Currently using or have used within three months before this trial: pramlintide, sibutramine, orlistat, zonisamide, topiramate, phenteremine, or metformin * Previous surgical treatment for obesity (excluding liposuction if performed more than one year before trial entry) * History of major depressive disorder or a PHQ-9 (Patient Health Questionnaire-9) score of more than 15 within the last 2 years or history of other severe psychiatric disorders or diagnosis of an eating disorder * Subjects with a lifetime history of a suicide attempt or history of any suicidal behavior within the past month before entry into the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percentage Change in Fasting Body Weight From Baseline | Week 0, week 56 | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. |
| Percentage of Subjects Who Maintained Their run-in Fasting Weight Loss From Week 0 | Week 0, week 56 | Subjects who had a weight regain less than or equal to 0.5% of weight from Week 0 were regarded as maintenance of run-in fasting weight loss. Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. |
| Percentage of Subjects Who Lost More Than or Equal to 5% of Fasting Body Weight From Week 0 | Week 0, week 56 | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Greater Than 50% of Fasting run-in Weight Loss Maintained From Week 0 | Week 0, week 56 | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. |
| Percentage of Subjects With Greater Than 75% of Fasting run-in Weight Loss Maintained From Week 0 | Week 0, week 56 | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. |
| Change From Baseline in Fasting Weight | Week 0, week 56 | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. |
| Change From Baseline in Fasting Weight for Subjects Completing the Main Trial Period and Entering the Follow-up Period | Week 0, week 68 | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. |
| Change From Baseline in Blood Pressure | Week 0, week 56 | — |
| Change From Baseline in Pulse | Week 0, week 56 | — |
| Change From Baseline in Fasting Lipid Profile: Triglycerides | Week 0, week 56 | Subjects were tested having fasted (consumed only water) since midnight the night before the visit. |
| Change From Baseline in Fasting Lipid Profile: Low Density Lipoprotein (LDL) Cholesterol | Week 0, week 56 | Subjects were tested having fasted (consumed only water) since midnight the night before the visit. |
| Change From Baseline in Fasting Lipid Profile: Total Cholesterol | Week 0, week 56 | Subjects were tested having fasted (consumed only water) since midnight the night before the visit. |
| Change From Baseline in Cardiovascular Biomarker: High Sensitivity C-reactive Protein (hsCRP) | Week 0, week 56 | — |
| Percentage of Subjects Who Lost More Than 10% of Fasting Body Weight From Week 0 | Week 0, week 56 | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. |
| Change From Baseline in Waist Circumference | Week 0, week 56 | — |
| Change From Baseline in Body Mass Index (BMI) | Week 0, week 56 | — |
| Change From Baseline in Glycaemic Control Parameter: HOMA-B (Homeostasis Model Assessment - Beta Cell Function) | Week 0, week 56 | Change in beta-cell function percent values from Week 0 (X%) to Week 56 (Y%) was calculated \[X% - Y%\]. Beta-cell function was derived from fasting plasma glucose readings in blood samples using the HOMA method, which is based on the assumption that normal-weight subjects without diabetes aged \<35 years have median beta-cell function indexed at 100%. |
| Change From Baseline in Glycaemic Control Parameter: HOMA-IR (Homeostasis Model Assessment - Insulin Resistance) | Week 0, week 56 | Change in insulin resistance values from Week 0 (X) to Week 56 (Y) was calculated \[X - Y\]. Insulin resistance was derived from fasting serum insulin levels in blood samples using the HOMA method, which is based on the assumption that normal-weight subjects without diabetes aged \<35 years have median insulin resistance indexed at 1.00. |
| Change From Baseline in Glycaemic Control Parameter: Fasting Plasma Glucose (FPG) | Week 0, week 56 | Subjects were tested having fasted (consumed only water) since midnight the night before the visit. |
| Change From Baseline in Glycaemic Control Parameter: Fasting Serum Insulin | Week 0, week 56 | Subjects were tested having fasted (consumed only water) since midnight the night before the visit. |
| Change From Baseline in Glycaemic Control Parameter: HbA1c (Glycosylated Haemoglobin) | Week 0, week 56 | Change in HbA1c percent values from Week 0 (X%) to Week 56 (Y%) was calculated \[X% - Y%\]. |
| Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications) | Week 0 and week 56 | Number of subjects using concomitant medications at Week 0 and Week 56, respectively |
| Binge Eating Scale Scores by Week and Severity | Week 0, week 50 and week 57 | Binge Eating Scale (BES) scores are based on responses to the Binge Eating Scale Questionnaire, a 16-item self-reporting diagnostic tool scaled 0-46 (Non-binging: 0-17; Moderate: 17-26; Severe: 27-46) |
| Percentage of Subjects Meeting Metabolic Syndrome Criteria: ATP (Adult Treatment Panel) III at Week 56 | Week 56 | Metabolic syndrome status required at least 3 of 5 criteria met: Waist circumference (men ≥102cm, women ≥88cm); Triglycerides \>1.7mmol/L; High density lipoprotein cholesterol (men \<0.9mmol/L, women \<1.1mmol/L) or on drug therapy; Blood pressure ≥130mmHg systolic or ≥85mmHg diastolic or on drug therapy; Fasting glucose ≥5.5mmol/L or on drug therapy. |
| Percentage of Subjects With Weight Regain (Fasting) More Than or Equal to 5% From Week 0 | Week 0, week 56 | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. |
| Percentage of Subjects With Weight Regain (Fasting) More Than or Equal to 10% From Week 0 | Week 0, week 56 | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. |
Countries
Canada, United States
Participant flow
Recruitment details
The trial was conducted at 26 sites in the United States and 10 sites in Canada.
Pre-assignment details
Subjects who lost at least 5% of screening body weight after 4 weeks and up to 12 weeks during the run-in were randomised in a 1:1 manner to receive either liraglutide 3.0 mg, or placebo for 56 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Lira 3.0 mg A 12-week run-in period where screened subjects were treated with a low calorie diet. Randomised subjects (those who lost more than or equal to 5% of screening body weight) were treated with liraglutide 3.0 mg, once daily, injected subcutaneously and instructed to follow a standard energy-restricted diet in the 56-week main trial period. Subjects discontinued treatment in the 12-week follow-up period. The starting dose of liraglutide was 0.6 mg, with weekly increments of 0.6 mg every 7 days until the target dose of 3.0 mg was reached | 212 |
| Placebo A 12-week run-in period where screened subjects were treated with a low calorie diet. Randomised subjects (those who lost more than or equal to 5% of screening body weight) were treated with liraglutide placebo, once daily, injected subcutaneously for 56 weeks and instructed to follow a standard energy-restricted diet in the 56-week main trial period. Subjects discontinued treatment in the 12-week follow-up period | 210 |
| Total | 422 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow up Period (Week 56-68) | Protocol Violation | 1 | 1 |
| Follow up Period (Week 56-68) | Unclassified | 5 | 4 |
| Main Trial Period Through Week 56 | Adverse Event | 18 | 18 |
| Main Trial Period Through Week 56 | Lack of Efficacy | 0 | 2 |
| Main Trial Period Through Week 56 | Protocol Violation | 8 | 5 |
| Main Trial Period Through Week 56 | Unclassified | 10 | 15 |
| Main Trial Period Through Week 56 | Withdrawal by Subject | 17 | 24 |
Baseline characteristics
| Characteristic | Total | Lira 3.0 mg | Placebo |
|---|---|---|---|
| Age, Continuous | 46.2 years STANDARD_DEVIATION 11.5 | 45.9 years STANDARD_DEVIATION 11.9 | 46.5 years STANDARD_DEVIATION 11 |
| Body Mass Index (BMI) at randomisation | 35.6 kg/m^2 STANDARD_DEVIATION 5.9 | 36.0 kg/m^2 STANDARD_DEVIATION 5.9 | 35.2 kg/m^2 STANDARD_DEVIATION 5.9 |
| Body Mass Index (BMI) at screening | 37.9 kg/m^2 STANDARD_DEVIATION 6.2 | 38.2 kg/m^2 STANDARD_DEVIATION 6.2 | 37.5 kg/m^2 STANDARD_DEVIATION 6.2 |
| Body Mass Index (BMI) group (kg/m^2) at screening 27-30 | 9 participants | 3 participants | 6 participants |
| Body Mass Index (BMI) group (kg/m^2) at screening 30-35 | 149 participants | 69 participants | 80 participants |
| Body Mass Index (BMI) group (kg/m^2) at screening 35-40 | 127 participants | 69 participants | 58 participants |
| Body Mass Index (BMI) group (kg/m^2) at screening Greater than or equal to 40 | 137 participants | 71 participants | 66 participants |
| Co-morbidity status Absent | 232 participants | 118 participants | 114 participants |
| Co-morbidity status Present | 190 participants | 94 participants | 96 participants |
| Co-morbidity status and Body Mass Index (BMI) Absent and BMI >=30 kg/m^2 | 232 participants | 118 participants | 114 participants |
| Co-morbidity status and Body Mass Index (BMI) Present and BMI (27-30) kg/m^2 | 9 participants | 3 participants | 6 participants |
| Co-morbidity status and Body Mass Index (BMI) Present and BMI >=30 kg/m^2 | 181 participants | 91 participants | 90 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 28 Participants | 17 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 394 Participants | 195 Participants | 199 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 1.67 meters STANDARD_DEVIATION 0.09 | 1.67 meters STANDARD_DEVIATION 0.09 | 1.67 meters STANDARD_DEVIATION 0.09 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 56 Participants | 32 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 7 Participants | 1 Participants |
| Race (NIH/OMB) White | 355 Participants | 170 Participants | 185 Participants |
| Sex: Female, Male Female | 343 Participants | 178 Participants | 165 Participants |
| Sex: Female, Male Male | 79 Participants | 34 Participants | 45 Participants |
| Smoking No | 380 participants | 192 participants | 188 participants |
| Smoking Yes | 42 participants | 20 participants | 22 participants |
| Weight at randomisation | 99.6 kg STANDARD_DEVIATION 21 | 100.4 kg STANDARD_DEVIATION 20.8 | 98.7 kg STANDARD_DEVIATION 21.2 |
| Weight at screening | 105.9 kg STANDARD_DEVIATION 22.1 | 106.7 kg STANDARD_DEVIATION 21.8 | 105.0 kg STANDARD_DEVIATION 22.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 177 / 212 | 163 / 210 |
| serious Total, serious adverse events | 9 / 212 | 5 / 210 |
Outcome results
Primary
Mean Percentage Change in Fasting Body Weight From Baseline
Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 3.0 mg | Mean Percentage Change in Fasting Body Weight From Baseline | -6.11 percentage | Standard Error 0.66 |
| Placebo | Mean Percentage Change in Fasting Body Weight From Baseline | -0.05 percentage | Standard Error 0.63 |
Comparison: The 3 co-primary endpoints (Outcome Measures 1, 2 and 3) were ranked (#1, 2, 3) and the hypotheses of equality between liraglutide and placebo for each were tested in a hierarchical manner; i.e. a conclusion of liraglutide superiority for a given co-primary endpoint could be drawn only if all preceding hypotheses of equality in the hierarchy had been rejected.p-value: <0.000195% CI: [-7.5, -4.62]ANCOVA
Primary
Percentage of Subjects Who Lost More Than or Equal to 5% of Fasting Body Weight From Week 0
Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lira 3.0 mg | Percentage of Subjects Who Lost More Than or Equal to 5% of Fasting Body Weight From Week 0 | 50.5 percentage of subjects |
| Placebo | Percentage of Subjects Who Lost More Than or Equal to 5% of Fasting Body Weight From Week 0 | 21.9 percentage of subjects |
Comparison: The 3 co-primary endpoints (Outcome Measures 1, 2 and 3) were ranked (#1, 2, 3) and the hypotheses of equality between liraglutide and placebo for each were tested in a hierarchical manner; i.e. a conclusion of liraglutide superiority for a given co-primary endpoint could be drawn only if all preceding hypotheses of equality in the hierarchy had been rejected.p-value: <0.000195% CI: [2.44, 6.09]Regression, Logistic
Primary
Percentage of Subjects Who Maintained Their run-in Fasting Weight Loss From Week 0
Subjects who had a weight regain less than or equal to 0.5% of weight from Week 0 were regarded as maintenance of run-in fasting weight loss. Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lira 3.0 mg | Percentage of Subjects Who Maintained Their run-in Fasting Weight Loss From Week 0 | 80.8 percentage of subjects |
| Placebo | Percentage of Subjects Who Maintained Their run-in Fasting Weight Loss From Week 0 | 47.9 percentage of subjects |
Comparison: The 3 co-primary endpoints (Outcome Measures 1, 2 and 3) were ranked (#1, 2, 3) and the hypotheses of equality between liraglutide and placebo for each were tested in a hierarchical manner; i.e. a conclusion of liraglutide superiority for a given co-primary endpoint could be drawn only if all preceding hypotheses of equality in the hierarchy had been rejected.p-value: <0.000195% CI: [3.01, 7.71]Regression, Logistic
Secondary
Binge Eating Scale Scores by Week and Severity
Binge Eating Scale (BES) scores are based on responses to the Binge Eating Scale Questionnaire, a 16-item self-reporting diagnostic tool scaled 0-46 (Non-binging: 0-17; Moderate: 17-26; Severe: 27-46)
Time frame: Week 0, week 50 and week 57
Population: Full Analysis Set (includes all randomised subjects 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 (MEAN) | Dispersion |
|---|---|---|---|---|
| Lira 3.0 mg | Binge Eating Scale Scores by Week and Severity | Week 0, baseline | 7.8 scores on a scale | Standard Deviation 5.6 |
| Lira 3.0 mg | Binge Eating Scale Scores by Week and Severity | Week 50 | 6.6 scores on a scale | Standard Deviation 5.6 |
| Lira 3.0 mg | Binge Eating Scale Scores by Week and Severity | Week 57 | 6.6 scores on a scale | Standard Deviation 5.8 |
| Placebo | Binge Eating Scale Scores by Week and Severity | Week 0, baseline | 7.8 scores on a scale | Standard Deviation 6.2 |
| Placebo | Binge Eating Scale Scores by Week and Severity | Week 50 | 8.6 scores on a scale | Standard Deviation 7 |
| Placebo | Binge Eating Scale Scores by Week and Severity | Week 57 | 6.9 scores on a scale | Standard Deviation 6.2 |
Secondary
Change From Baseline in Blood Pressure
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects 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 (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Lira 3.0 mg | Change From Baseline in Blood Pressure | Change in Systolic Blood Pressure | 1.31 mmHg | Standard Error 0.9 |
| Lira 3.0 mg | Change From Baseline in Blood Pressure | Change in Diastolic Blood Pressure | 1.81 mmHg | Standard Error 0.64 |
| Placebo | Change From Baseline in Blood Pressure | Change in Systolic Blood Pressure | 4.03 mmHg | Standard Error 0.87 |
| Placebo | Change From Baseline in Blood Pressure | Change in Diastolic Blood Pressure | 2.15 mmHg | Standard Error 0.61 |
Comparison: Analysis is of treatment contrast, change in systolic blood pressure.p-value: 0.006895% CI: [-4.69, -0.76]ANCOVA
Comparison: Analysis is of treatment contrast, change in diastolic blood pressure.p-value: 0.638695% CI: [-1.74, 1.07]ANCOVA
Secondary
Change From Baseline in Body Mass Index (BMI)
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 3.0 mg | Change From Baseline in Body Mass Index (BMI) | -1.90 kg/m^2 | Standard Error 0.22 |
| Placebo | Change From Baseline in Body Mass Index (BMI) | 0.15 kg/m^2 | Standard Error 0.21 |
p-value: <0.000195% CI: [-2.53, -1.57]ANCOVA
Secondary
Change From Baseline in Cardiovascular Biomarker: High Sensitivity C-reactive Protein (hsCRP)
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 3.0 mg | Change From Baseline in Cardiovascular Biomarker: High Sensitivity C-reactive Protein (hsCRP) | -11.31 nmol/L | Standard Error 4.62 |
| Placebo | Change From Baseline in Cardiovascular Biomarker: High Sensitivity C-reactive Protein (hsCRP) | 1.70 nmol/L | Standard Error 4.51 |
p-value: 0.014195% CI: [-23.4, -2.64]ANCOVA
Secondary
Change From Baseline in Fasting Lipid Profile: Low Density Lipoprotein (LDL) Cholesterol
Subjects were tested having fasted (consumed only water) since midnight the night before the visit.
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 3.0 mg | Change From Baseline in Fasting Lipid Profile: Low Density Lipoprotein (LDL) Cholesterol | 0.24 mmol/L | Standard Error 0.05 |
| Placebo | Change From Baseline in Fasting Lipid Profile: Low Density Lipoprotein (LDL) Cholesterol | 0.33 mmol/L | Standard Error 0.05 |
p-value: 0.109895% CI: [-0.2, 0.02]ANCOVA
Secondary
Change From Baseline in Fasting Lipid Profile: Total Cholesterol
Subjects were tested having fasted (consumed only water) since midnight the night before the visit.
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 3.0 mg | Change From Baseline in Fasting Lipid Profile: Total Cholesterol | 0.22 mmol/L | Standard Error 0.06 |
| Placebo | Change From Baseline in Fasting Lipid Profile: Total Cholesterol | 0.33 mmol/L | Standard Error 0.06 |
p-value: 0.114995% CI: [-0.24, 0.03]ANCOVA
Secondary
Change From Baseline in Fasting Lipid Profile: Triglycerides
Subjects were tested having fasted (consumed only water) since midnight the night before the visit.
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 3.0 mg | Change From Baseline in Fasting Lipid Profile: Triglycerides | 0.02 mmol/L | Standard Error 0.04 |
| Placebo | Change From Baseline in Fasting Lipid Profile: Triglycerides | 0.12 mmol/L | Standard Error 0.04 |
p-value: 0.03195% CI: [-0.2, -0.01]ANCOVA
Secondary
Change From Baseline in Fasting Weight
Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 3.0 mg | Change From Baseline in Fasting Weight | -5.7 kg | Standard Error 0.66 |
| Placebo | Change From Baseline in Fasting Weight | 0.16 kg | Standard Error 0.63 |
p-value: <0.000195% CI: [-7.3, -4.43]ANCOVA
Secondary
Change From Baseline in Fasting Weight for Subjects Completing the Main Trial Period and Entering the Follow-up Period
Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Time frame: Week 0, week 68
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 3.0 mg | Change From Baseline in Fasting Weight for Subjects Completing the Main Trial Period and Entering the Follow-up Period | -3.83 kg | Standard Error 0.82 |
| Placebo | Change From Baseline in Fasting Weight for Subjects Completing the Main Trial Period and Entering the Follow-up Period | 0.41 kg | Standard Error 0.78 |
p-value: <0.000195% CI: [-6.04, -2.43]ANCOVA
Secondary
Change From Baseline in Glycaemic Control Parameter: Fasting Plasma Glucose (FPG)
Subjects were tested having fasted (consumed only water) since midnight the night before the visit.
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 3.0 mg | Change From Baseline in Glycaemic Control Parameter: Fasting Plasma Glucose (FPG) | -0.52 mmol/L | Standard Error 0.05 |
| Placebo | Change From Baseline in Glycaemic Control Parameter: Fasting Plasma Glucose (FPG) | -0.14 mmol/L | Standard Error 0.05 |
p-value: <0.000195% CI: [-0.5, -0.26]ANCOVA
Secondary
Change From Baseline in Glycaemic Control Parameter: Fasting Serum Insulin
Subjects were tested having fasted (consumed only water) since midnight the night before the visit.
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 3.0 mg | Change From Baseline in Glycaemic Control Parameter: Fasting Serum Insulin | 0.50 pmol/L | Standard Error 0.67 |
| Placebo | Change From Baseline in Glycaemic Control Parameter: Fasting Serum Insulin | 2.35 pmol/L | Standard Error 0.65 |
p-value: 0.014795% CI: [-3.34, -0.37]ANCOVA
Secondary
Change From Baseline in Glycaemic Control Parameter: HbA1c (Glycosylated Haemoglobin)
Change in HbA1c percent values from Week 0 (X%) to Week 56 (Y%) was calculated \[X% - Y%\].
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 3.0 mg | Change From Baseline in Glycaemic Control Parameter: HbA1c (Glycosylated Haemoglobin) | -0.14 percentage point | Standard Error 0.03 |
| Placebo | Change From Baseline in Glycaemic Control Parameter: HbA1c (Glycosylated Haemoglobin) | 0.13 percentage point | Standard Error 0.03 |
p-value: <0.000195% CI: [-0.33, -0.21]ANCOVA
Secondary
Change From Baseline in Glycaemic Control Parameter: HOMA-B (Homeostasis Model Assessment - Beta Cell Function)
Change in beta-cell function percent values from Week 0 (X%) to Week 56 (Y%) was calculated \[X% - Y%\]. Beta-cell function was derived from fasting plasma glucose readings in blood samples using the HOMA method, which is based on the assumption that normal-weight subjects without diabetes aged \<35 years have median beta-cell function indexed at 100%.
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 3.0 mg | Change From Baseline in Glycaemic Control Parameter: HOMA-B (Homeostasis Model Assessment - Beta Cell Function) | 8.51 percent change | Standard Error 2.33 |
| Placebo | Change From Baseline in Glycaemic Control Parameter: HOMA-B (Homeostasis Model Assessment - Beta Cell Function) | 6.16 percent change | Standard Error 2.27 |
p-value: 0.368995% CI: [-2.79, 7.49]ANCOVA
Secondary
Change From Baseline in Glycaemic Control Parameter: HOMA-IR (Homeostasis Model Assessment - Insulin Resistance)
Change in insulin resistance values from Week 0 (X) to Week 56 (Y) was calculated \[X - Y\]. Insulin resistance was derived from fasting serum insulin levels in blood samples using the HOMA method, which is based on the assumption that normal-weight subjects without diabetes aged \<35 years have median insulin resistance indexed at 1.00.
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 3.0 mg | Change From Baseline in Glycaemic Control Parameter: HOMA-IR (Homeostasis Model Assessment - Insulin Resistance) | -0.01 proportion | Standard Error 0.03 |
| Placebo | Change From Baseline in Glycaemic Control Parameter: HOMA-IR (Homeostasis Model Assessment - Insulin Resistance) | 0.08 proportion | Standard Error 0.03 |
p-value: 0.005395% CI: [-0.16, -0.03]ANCOVA
Secondary
Change From Baseline in Pulse
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 3.0 mg | Change From Baseline in Pulse | 4.12 beats/minute | Standard Error 0.68 |
| Placebo | Change From Baseline in Pulse | 3.15 beats/minute | Standard Error 0.65 |
p-value: 0.196895% CI: [-0.51, 2.45]ANCOVA
Secondary
Change From Baseline in Waist Circumference
Time frame: Week 0, week 56
Population: Last Observation Carried Forward, Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lira 3.0 mg | Change From Baseline in Waist Circumference | -4.36 cm | Standard Error 0.62 |
| Placebo | Change From Baseline in Waist Circumference | -0.86 cm | Standard Error 0.59 |
p-value: <0.000195% CI: [-4.84, -2.15]ANCOVA
Secondary
Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications)
Number of subjects using concomitant medications at Week 0 and Week 56, respectively
Time frame: Week 0 and week 56
Population: Full Analysis Set (includes all randomised subjects 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) |
|---|---|---|---|
| Lira 3.0 mg | Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications) | Antihypertensive drug - Week 0 | 65 Subjects |
| Lira 3.0 mg | Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications) | Antihypertensive drug - Week 56 | 63 Subjects |
| Lira 3.0 mg | Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications) | Antipsychotic drug - Week 0 | 18 Subjects |
| Lira 3.0 mg | Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications) | Antipsychotic drug - Week 56 | 20 Subjects |
| Lira 3.0 mg | Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications) | Lipid lowering drug - Week 0 | 45 Subjects |
| Lira 3.0 mg | Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications) | Lipid lowering drug - Week 56 | 52 Subjects |
| Placebo | Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications) | Lipid lowering drug - Week 0 | 45 Subjects |
| Placebo | Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications) | Antihypertensive drug - Week 0 | 66 Subjects |
| Placebo | Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications) | Antipsychotic drug - Week 56 | 29 Subjects |
| Placebo | Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications) | Antihypertensive drug - Week 56 | 63 Subjects |
| Placebo | Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications) | Lipid lowering drug - Week 56 | 50 Subjects |
| Placebo | Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications) | Antipsychotic drug - Week 0 | 25 Subjects |
Secondary
Percentage of Subjects Meeting Metabolic Syndrome Criteria: ATP (Adult Treatment Panel) III at Week 56
Metabolic syndrome status required at least 3 of 5 criteria met: Waist circumference (men ≥102cm, women ≥88cm); Triglycerides \>1.7mmol/L; High density lipoprotein cholesterol (men \<0.9mmol/L, women \<1.1mmol/L) or on drug therapy; Blood pressure ≥130mmHg systolic or ≥85mmHg diastolic or on drug therapy; Fasting glucose ≥5.5mmol/L or on drug therapy.
Time frame: Week 56
Population: Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lira 3.0 mg | Percentage of Subjects Meeting Metabolic Syndrome Criteria: ATP (Adult Treatment Panel) III at Week 56 | 31.4 percentage of subjects |
| Placebo | Percentage of Subjects Meeting Metabolic Syndrome Criteria: ATP (Adult Treatment Panel) III at Week 56 | 36.7 percentage of subjects |
p-value: 0.119995% CI: [0.36, 1.12]Regression, Logistic
Secondary
Percentage of Subjects Who Lost More Than 10% of Fasting Body Weight From Week 0
Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Time frame: Week 0, week 56
Population: Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lira 3.0 mg | Percentage of Subjects Who Lost More Than 10% of Fasting Body Weight From Week 0 | 26.1 percentage of subjects |
| Placebo | Percentage of Subjects Who Lost More Than 10% of Fasting Body Weight From Week 0 | 6.3 percentage of subjects |
p-value: <0.000195% CI: [2.79, 10.08]Regression, Logistic
Secondary
Percentage of Subjects With Greater Than 50% of Fasting run-in Weight Loss Maintained From Week 0
Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Time frame: Week 0, week 56
Population: Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lira 3.0 mg | Percentage of Subjects With Greater Than 50% of Fasting run-in Weight Loss Maintained From Week 0 | 93.2 percentage of subjects |
| Placebo | Percentage of Subjects With Greater Than 50% of Fasting run-in Weight Loss Maintained From Week 0 | 70.9 percentage of subjects |
p-value: <0.000195% CI: [3.12, 10.98]Regression, Logistic
Secondary
Percentage of Subjects With Greater Than 75% of Fasting run-in Weight Loss Maintained From Week 0
Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Time frame: Week 0, week 56
Population: Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lira 3.0 mg | Percentage of Subjects With Greater Than 75% of Fasting run-in Weight Loss Maintained From Week 0 | 87.4 percentage of subjects |
| Placebo | Percentage of Subjects With Greater Than 75% of Fasting run-in Weight Loss Maintained From Week 0 | 54.4 percentage of subjects |
p-value: <0.000195% CI: [3.65, 9.92]Regression, Logistic
Secondary
Percentage of Subjects With Weight Regain (Fasting) More Than or Equal to 10% From Week 0
Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Time frame: Week 0, week 56
Population: Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lira 3.0 mg | Percentage of Subjects With Weight Regain (Fasting) More Than or Equal to 10% From Week 0 | 0 percentage of subjects |
| Placebo | Percentage of Subjects With Weight Regain (Fasting) More Than or Equal to 10% From Week 0 | 2.9 percentage of subjects |
Secondary
Percentage of Subjects With Weight Regain (Fasting) More Than or Equal to 5% From Week 0
Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Time frame: Week 0, week 56
Population: Full Analysis Set (includes all randomised subjects exposed to at least 1 dose of trial product and with at least 1 post-randomisation assessment of any efficacy endpoint.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lira 3.0 mg | Percentage of Subjects With Weight Regain (Fasting) More Than or Equal to 5% From Week 0 | 1.9 percentage of subjects |
| Placebo | Percentage of Subjects With Weight Regain (Fasting) More Than or Equal to 5% From Week 0 | 17.5 percentage of subjects |
p-value: <0.000195% CI: [0.03, 0.26]Regression, Logistic