SCALE™ IBT: Effect and Safety of Liraglutide 3.0 mg as an Adjunct to Intensive Behaviour Therapy for Obesity in a Non-specialist Setting

Sponsor

Novo Nordisk A/S (Industry)

Overall Status

Completed

CT.gov ID

NCT02963935

Collaborator

(none)

282

Enrollment

Locations

Arms

16.4

Actual Duration (Months)

28.2

Patients Per Site

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial is conducted in the United States of America (USA). The purpose of the trial is to investigate the effect and safety of liraglutide 3.0 mg as an adjunct to intensive behaviour therapy for obesity in a non-specialist setting (IBT-CMS: Intensive Behaviour Therapy for obesity in a primary care setting according to Centers for Medicare & Medicaid Services (CMS) visit schedule).

Condition or Disease	Intervention/Treatment	Phase
Metabolism and Nutrition Disorder Obesity	Drug: liraglutide Drug: placebo Behavioral: CMS Intensive Behavior Therapy	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

282 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Effect and Safety of Liraglutide 3.0 mg as an Adjunct to Intensive Behaviour Therapy for Obesity in a Non-specialist Setting

Actual Study Start Date :

Feb 6, 2017

Actual Primary Completion Date :

May 23, 2018

Actual Study Completion Date :

Jun 19, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Liraglutide	Drug: liraglutide Administered subcutaneously (s.c., under the skin) once daily for 56 weeks. Dose gradually increased to 3.0 mg Behavioral: CMS Intensive Behavior Therapy Intensive Behaviour Therapy for obesity
Placebo Comparator: Placebo	Drug: placebo Administered subcutaneously (s.c., under the skin) once daily for 56 weeks. Dose gradually increased to 3.0 mg Behavioral: CMS Intensive Behavior Therapy Intensive Behaviour Therapy for obesity

Arm

Intervention/Treatment

Experimental: Liraglutide

Drug: liraglutide

Administered subcutaneously (s.c., under the skin) once daily for 56 weeks. Dose gradually increased to 3.0 mg

Behavioral: CMS Intensive Behavior Therapy

Intensive Behaviour Therapy for obesity

Placebo Comparator: Placebo

Drug: placebo

Administered subcutaneously (s.c., under the skin) once daily for 56 weeks. Dose gradually increased to 3.0 mg

Behavioral: CMS Intensive Behavior Therapy

Intensive Behaviour Therapy for obesity

Outcome Measures

Primary Outcome Measures

Change in Body Weight (%) [Week 0, week 56]
Observed mean change in body weight from baseline (week 0) to week 56 was evaluated for two different observation periods. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which subjects are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs). The test of superiority of liraglutide to placebo for the treatment policy estimand was tested in a hierarchical manner for the two primary and the consequent 7 confirmatory secondary endpoints presented.
Proportion of Subjects Losing at Least 5% of Baseline Body Weight at Week 56 [Week 56]
The estimated mean percentage of subjects losing at least 5% of baseline body weight at week 56 is presented. The endpoint was evaluated based on in-trial data and on-drug data.

Secondary Outcome Measures

Proportion of Subjects Losing More Than 10% of Baseline Body Weight at Week 56 [Week 56]
The estimated mean percentage of subjects losing more than 10% of baseline body weight at week 56 is presented. The endpoint was evaluated based on in-trial data and on-drug data.
Proportion of Subjects Losing More Than 15% of Baseline Body Weight at Week 56 [Week 56]
The estimated mean percentage of subjects losing more than 15% of baseline body weight at week 56 is presented. The endpoint was evaluated based on in-trial data and on-drug data.
Proportion of Subjects Losing 4% or More of Baseline Body Weight [Week 16]
The estimated mean percentage of subjects losing 4% or more of baseline body weight at week 16 is presented. The endpoint was evaluated for treatment policy estimand (in-trial data).
Change in Waist Circumference (cm) [Week 0, week 56]
Observed mean change from baseline in waist circumference. The endpoint was evaluated based on in-trial data and on-drug data.
Change in Short Form-36 (SF-36) v2.0 Acute, Physical Functioning Score [Week 0, week 56]
SF-36 is a 36-item patient-reported survey of patient health that measures the subject's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in SF-36 physical functioning score is presented. A positive change score indicates an improvement since baseline. The endpoint was evaluated based on in-trial data and on-drug data.
Change in IWQoL-Lite for CT, Physical Function Domain (5-items) Score [Week 0, week 56]
Observed mean change in Impact of Weight on Quality of Life-Lite for Clinical Trials Version (IWQoL-Lite for CT ) score. IWQoL-Lite for CT (Weight on Quality of Life-Lite for Clinical Trial Version) is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. The endpoint was evaluated based on in-trial data and on-drug data.
Change in Six Minutes Walking Distance Test (6MWT) [Week 0, week 56]
Observed mean change from baseline in 6 minutes walking distance test. The 6MWT is a common test of functional exercise capacity that assesses the distance a subject can walk in 6 minutes. The endpoint was evaluated based on in-trial data and on-drug data.
Change From Baseline in HbA1c (%) [Week 0, week 56]
Observed mean change from baseline to week 56 in glycosylated haemoglobin (HbA1c). Results based on FAS in-trial data is presented.
Change From Baseline in FPG (mg/dL) [Week 0, week 56]
Observed mean change from baseline (week 0) in fasting plasma glucose (FPG). Results based on FAS in-trial data is presented.
Change From Baseline sBP (mmHg) [Week 0, week 56]
Observed mean change in systolic blood pressure from baseline to week 56.
Change From Baseline dBP (mmHg) [Week 0, week 56]
Observed mean change from baseline (week 0) to week 56 in diastolic blood pressure (dBP). Results based on FAS in-trial data is presented.
Change From Baseline in Lipids -Total Cholesterol [Week 0, week 56]
Observed mean change from baseline (week 0) to week 56 in total cholesterol (TC). Results based on FAS in-trial data is presented.
Change From Baseline in Lipids - LDL Cholesterol [Week 0, week 56]
Observed mean change from baseline in low density cholesterol (LDL) from baseline (week 0) to week 56. Results based on FAS in-trial data is presented.
Change From Baseline in Lipids - HDL Cholesterol [Week 0, week 56]
Observed mean change from baseline in high density (HDL) cholesterol from baseline (week 0) to week 56. Results based on FAS in-trial data is presented.
Change From Baseline in Lipids - VLDL Cholesterol [Week 0, week 56]
Observed mean change from baseline in very low density cholesterol (VLDL) from baseline (week 0) to week 56. Results based on FAS in-trial data is presented.
Change From Baseline in Lipids - TG [Week 0, week 56]
Observed mean change from baseline in triglyceride (TG) from baseline (week 0) to week 56. Results based on FAS in-trial data is presented.
Change From Baseline in Lipids - FFA [Week 0, week 56]
Observed mean change from baseline in free fatty acids (FFA) from baseline (week 0) to week 56. Results based on FAS in-trial data is presented.
Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains) [Week 0, week 56]
SF-36 is a 36-item patient-reported survey of patient health that measures the subject's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in in the sub-domain scores is presented. A positive change score indicates an improvement since baseline. Results are evaluated based on in-trial data.
Change in Short Form-36 v2.0 Acute (SF-36) (Physical Component Summary (PCS)) [Week 0, week 56]
Observed mean change from baseline (week 0) to week 56 in short form 36 v2.0 acute domain physical component summary (PCS). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in SF-36 physical component summary (PCS) score is presented. A positive change score indicates an improvement since baseline. The endpoint was evaluated based on in-trial data and on-drug data.
Change in Short Form-36 v2.0 Acute (SF-36) (Mental Component Summary (MCS) [Week 0, week 56]
Observed mean change from baseline (week 0) to week 56 in short form 36 v2.0 acute domain mental component summary (MCS). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in SF-36 mental component summary is presented. A positive change score indicates an improvement since baseline. The endpoint was evaluated based on in-trial data and on-drug data.
Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Pain/Discomfort Domain Score [Week 0, week 56]
Observed mean change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT) domain pain and discomfort. IWQoL-Lite for CT (Weight on Quality of Life-Lite for Clinical Trial Version) is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. Results based on FAS in-trial data is presented.
Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Psychosocial Domain Score [Week 0, week 56]
Observed mean change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT) psychosocial domain. IWQoL-Lite for CT (Weight on Quality of Life-Lite for Clinical Trial Version) is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. Results based on FAS in-trial data is presented.
Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Total Score [Week 0, week 56]
Observed mean change from baseline (week 0) to week 56 in IWQoL-Lite for CT total score. IWQoL-Lite for CT (Weight on Quality of Life-Lite for Clinical Trial Version) is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. Results based on FAS in-trial data is presented.
Change in Weight Related Sign and Symptom (WRSS) Measure, Total Score [Week 0, week 56]
Observed mean change from baseline (week 0) to week 56 in WRSS measure, total score. The WRSS measures the presence and bothersome associated with weight-related symptoms. The WRSS questionnaire was not validated until after database lock. Therefore the total score couldn't be calculated and the supportive secondary endpoint "Weight related sign and symptom (WRSS) measure, total score" couldn't be analysed.
Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 4.3 T-score Points Increase From Baseline in SF-36 Physical Functioning Score [Week 56]
Percentage of subjects who achieved ≥ 4.3 T-score points increase from baseline in SF-36 physical functioning score at week 56 is presented. Results based on FAS in-trial data is presented.
Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 3.8 T-score Points Increase From Baseline in SF-36 Physical Component Score [Week 56]
Percentage of subjects who achieved ≥ 3.8 T-score points increase from baseline in SF-36 physical component score at week 56 is presented. Results based on FAS in-trial data is presented.
Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 4.6 T-score Points Increase From Baseline in SF-36 Mental Component Score [Week 56]
Percentage of subjects who achieved ≥ 4.6 T-score points increase from baseline in SF-36 mental component score at week 56 is presented. Results based on FAS in-trial data is presented.
Responder Definition Value for IWQoL-Lite for CT Physical Function Domain (5-items) Score [Week 56]
Responder definition value for IWQoL-Lite for CT physical function domain (5-items) score' was defined as '≥ 20 responder definition value for IWQoL-Lite for CT physical function domain (5-items) score. Percentage of subjects considered IWQoL-Lite for CT physical function domain score responders (increase of ≥20 points) at week 56 is presented. Results based on FAS in-trial data is presented.
Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Trial Product [Week 0, week 56]
Adherence to trial product is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to trial product is presented.
Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet [Week 0, week 56]
Adherence to caloric diet is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to caloric diet is presented.
Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Physical Activity [Week 0, week 56]
Adherence to physical activity is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to physical activity is presented.
Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet and Physical Activity [Week 0, week 56]
Adherence to caloric diet and physical activity is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to caloric diet and physical activity is presented.
Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet, Physical Activity and Trial Product [Week 0, week 56]
Adherence to caloric diet, physical activity and trial product is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to caloric diet, physical activity and trial product is presented.
AEs From Randomisation Until and Including the Follow-up Period [Week 0 to week 56+30 days]
Number of adverse events from randomisation to until the end of the post-treatment follow-up period (30 days). Results based on SAS on-drug data is presented.
Change in Physical Examination [Week 1, week 56]
Observed change from baseline to week 56 in physical examination are categorised under parameters namely abdomen, gastrointestinal system, cardiovascular system, central and peripheral nervous system, general appearence, head, ears, eyes, nose, throat and neck, lymph node palpation, musculoskeletal system, respiratory system, skin and thyroid gland. The percentage of subjects assessed as normal, abnormal not clinically significant and abnormal clinically significant at baseline and week 56 is presented.
Change in Resting Pulse [Week 0, week 56]
Observed mean change in pulse rate measured at resting position is presented.
Change in ECG [Week -1, week 56]
The ECGs were interpreted by the investigator at baseline (week -1) and week 56 and categorised as normal, abnormal NCS or abnormal CS. Number of subjects in each ECG category at baseline and week 56 are presented.
Change in Laboratory Measurements: Haematology (Haemoglobin Blood) [Week 0, week 56]
Observed mean change from baseline in haematological parameter blood haemoglobin.
Change in Laboratory Measurements: Haematology (Haematocrit Blood) [Week 0, week 56]
Observed mean change from baseline in haematological parameter blood haematocrit. Haematocrit is presented as the percentage of red blood cells in total blood. Results based on SAS on-drug data is presented.
Change in Laboratory Measurements: Haematology (Erythrocytes) [Week 0, week 56]
Observed mean change from baseline in haematological parameter - erythrocytes.
Change in Laboratory Measurements: Haematology (Thrombocytes and Leukocytes) [Week 0, week 56]
Observed mean change from baseline in haematological parameters - thrombocytss and leukocytes.
Change in Laboratory Measurements: Biochemistry (Albumin) [Week 0, week 56]
Observed mean change from baseline in biochemical parameter - albumin. Results based on SAS on-drug data is presented.
Change in Laboratory Measurements: Biochemistry (Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase) [Week 0, week 56]
Observed mean change from baseline in biochemical parameters - alkaline phosphatase, alanine aminotransferase, amylase, aspartate aminotransferase and lipase. Results based on SAS on-drug data is presented.
Change in Laboratory Measurements: Biochemistry (Bilirubin and Creatinine) [Week 0, week 56]
Observed mean change from baseline in biochemical parameters - bilirubin and creatinine. Results based on SAS on-drug data is presented.
Change in Laboratory Measurements: Biochemistry (Total Calcium, Pottassium, Sodium and Urea) [Week 0, week 56]
Observed mean change from baseline in biochemical parameters - total calcium, pottassium, sodium and urea. Results based on SAS on-drug data is presented.
Change in Laboratory Measurements: Biochemistry (C-reactive Protein and Uric Acid) [Week 0, week 56]
Observed mean change from baseline in biochemical parameters - high sensitive c-reactive protein and uric acid. Results based on SAS on-drug data is presented.
Change in Laboratory Measurements: Biochemistry (Glomerular Filtration Rate, Serum) [Week 0, week 56]
Observed mean change from baseline in biochemical parameters - estimated glomerular filtration rate. Serum GFR is estimated using MDRD formula . Results based on SAS on-drug data is presented.
Change in Laboratory Measurements: Biochemistry (Calcitonin) [Week 0, week 56]
Observed mean change from baseline in biochemical parameter - calcitonin. Results based on SAS on-drug data is presented.
Change in Laboratory Measurements: Biochemistry (Thyroid Stimulating Hormone) [Week 0, week 56]
Observed mean change from baseline in biochemical parameters - thyroid stimulating hormone. Results based on SAS on-drug data is presented.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
BMI above or equal to 30 kg/m^2
Male or female, age 18 years or older at the time of signing informed consent

Exclusion Criteria:

HbA1c (glycosylated haemoglobin) above or equal to 6.5% (at screening visit), or diagnosis of type 1 or type 2 diabetes mellitus
Recent history of cardiovascular disease (myocardial infarction or stroke within the past 6 months), severe congestive heart failure (NYHA class III, IV), or second degree or greater heart block
Personal or family history of Medullary Thyroid Carcinoma (MTC), or Multiple Endocrine Neoplasia type 2 (MEN2)
Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice)
Use in past 90 days of medications known to induce significant weight loss (e.g., prescription weight loss medications) or weight gain (e.g., chronic use of oral steroids, second generation antipsychotics)
History of pancreatitis (acute or chronic)
History of major depressive disorder within the past 2 years
Any lifetime history of a suicide attempt
Inadequately treated blood pressure defined as Grade 3 hypertension or higher (Systolic above or equal to 180 mmHg or diastolic above or equal to 110 mmHg)
History of malignancy (except for non-melanoma skin cancer) within the past 5 years

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32205
2	Novo Nordisk Investigational Site	Plantation	Florida	United States	33324
3	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60607
4	Novo Nordisk Investigational Site	Greensboro	North Carolina	United States	27408
5	Novo Nordisk Investigational Site	Salisbury	North Carolina	United States	28144
6	Novo Nordisk Investigational Site	Wadsworth	Ohio	United States	44281
7	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19104-3317
8	Novo Nordisk Investigational Site	Charleston	South Carolina	United States	29425
9	Novo Nordisk Investigational Site	Dallas	Texas	United States	75251
10	Novo Nordisk Investigational Site	Arlington	Virginia	United States	22206

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

None specified.

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Novo Nordisk A/S

ClinicalTrials.gov Identifier:

NCT02963935

Other Study ID Numbers:

NN8022-4274
U1111-1177-5059

First Posted:

Nov 15, 2016

Last Update Posted:

Mar 11, 2020

Last Verified:

Feb 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Obesity

Nutrition Disorders

Liraglutide

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 17 sites in the United States.
Pre-assignment Detail	All the subjects received Intensive Behaviour Therapy (IBT) for obesity in a primary care setting according to Centers for Medicare & Medicaid Services (CMS) visit schedule during the trial.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Period Title: Overall Study
STARTED	142	140
COMPLETED	114	103
NOT COMPLETED	28	37

Baseline Characteristics

Arm/Group Title	Liraglutide 3.0 mg	Placebo	Total
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.	Total of all reporting groups
Overall Participants	142	140	282
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	45.4 (11.6)	49 (11.2)	47.2 (11.5)
Sex: Female, Male (Count of Participants)
Female	119 83.8%	116 82.9%	235 83.3%
Male	23 16.2%	24 17.1%	47 16.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 1.4%	3 2.1%	5 1.8%
Native Hawaiian or Other Pacific Islander	1 0.7%	0 0%	1 0.4%
Black or African American	27 19%	22 15.7%	49 17.4%
White	112 78.9%	115 82.1%	227 80.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Body weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	108.5 (22.1)	106.7 (22.0)	107.6 (22.0)

Outcome Measures

1. Primary Outcome

Title	Change in Body Weight (%)
Description	Observed mean change in body weight from baseline (week 0) to week 56 was evaluated for two different observation periods. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which subjects are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs). The test of superiority of liraglutide to placebo for the treatment policy estimand was tested in a hierarchical manner for the two primary and the consequent 7 confirmatory secondary endpoints presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
In-trial observation period	-7.4 (7.9)	-4.0 (7.4)
On-drug observation period	-9.1 (7.4)	-4.8 (7.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Treatrment policy estimand. The hypothesis and the alternative are: H: μliraglutide ≥ μplacebo against the alternative HA: μliraglutide < μplacebo. μliraglutide and μplacebo denote the true mean of % weight change for liraglutide 3.0 mg and placebo group, respectively. Week 56 responses were analysed using an analysis of covariance model with treatment, BMI groups, and sex as factors and baseline body weight as covariate.
	Type of Statistical Test	Superiority
	Comments	The treatment policy estimand evaluated the treatment effect (liraglutide 3.0 mg vs placebo) at week 56 for all randomised subjects regardless of premature discontinuation of trial product.

Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANCOVA
	Comments	Missing observations were imputed from the placebo arm based on a jump to reference (x100) multiple imputation approach.

Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-3.45
	Confidence Interval	(2-Sided) 95% -5.31 to -1.59
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg - placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Hypothetical estimand. Analysis of on-drug data before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups, and sex as factors and baseline body weight as covariate, all nested within visit.
	Type of Statistical Test	Other
	Comments	The hypothetical estimand evaluated the treatment effect (liraglutide 3.0 mg vs placebo) for all randomised subjects assuming that all subjects remained on trial product (on-treatment principle)

Statistical Test of Hypothesis	p-Value	0.0000
	Comments
	Method	Mixed models repeated measurement (MMRM)
	Comments

Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-4.59
	Confidence Interval	(2-Sided) 95% -6.54 to -2.64
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg - placebo

2. Primary Outcome

Title	Proportion of Subjects Losing at Least 5% of Baseline Body Weight at Week 56
Description	The estimated mean percentage of subjects losing at least 5% of baseline body weight at week 56 is presented. The endpoint was evaluated based on in-trial data and on-drug data.
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
In-trial observation period	61.47 43.3%	38.82 27.7%
On-drug observation period	64.08 45.1%	38.57 27.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Treatment policy estimand. Week 56 responses were analysed using a logistic regression model with treatment, BMI groups, and sex as factors and baseline body weight as covariate. Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.51
	Confidence Interval	(2-Sided) 95% 1.53 to 4.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg/Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Hypothetical estimand. Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups, and sex as factors and baseline body weight as covariate, all nested within visit. The MMRM was used to classify responders and analysed with a logistic regression with treatment as the only factor.
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0000
	Comments
	Method	Mixed models repeated measurement (MMRM)
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.84
	Confidence Interval	(2-Sided) 95% 1.75 to 4.61
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg/placebo

3. Secondary Outcome

Title	Proportion of Subjects Losing More Than 10% of Baseline Body Weight at Week 56
Description	The estimated mean percentage of subjects losing more than 10% of baseline body weight at week 56 is presented. The endpoint was evaluated based on in-trial data and on-drug data.
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
In-trial observation period	30.45 21.4%	19.75 14.1%
On-drug observation period	33.80 23.8%	19.29 13.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Treatment policy estimand. Week 56 responses were analysed using a logistic regression model with treatment, BMI groups, and sex as factors and baseline body weight as covariate. Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x10000) imputation approach.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0469
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.78
	Confidence Interval	(2-Sided) 95% 1.01 to 3.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg/Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Hypothetical estimand. Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups, and sex as factors and baseline body weight as covariate, all nested within visit. The MMRM was used to classify responders and analysed with a logistic regression with treatment as the only factor.
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0063
	Comments
	Method	Mixed models repeated measurement (MMRM)
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.14
	Confidence Interval	(2-Sided) 95% 1.24 to 3.69
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg/placebo

4. Secondary Outcome

Title	Proportion of Subjects Losing More Than 15% of Baseline Body Weight at Week 56
Description	The estimated mean percentage of subjects losing more than 15% of baseline body weight at week 56 is presented. The endpoint was evaluated based on in-trial data and on-drug data.
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
In-trial observation period	18.11 12.8%	8.92 6.4%
On-drug observation period	20.42 14.4%	8.57 6.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Treatment policy estimand. Week 56 responses were analysed using a logistic regression model with treatment, BMI groups, and sex as factors and baseline body weight as covariate. Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0311
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.26
	Confidence Interval	(2-Sided) 95% 1.08 to 4.74
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg/Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Hypothetical estimand. Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups, and sex as factors and baseline body weight as covariate, all nested within visit. The MMRM was used to classify responders and analysed with a logistic regression with treatment as the only factor.
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0060
	Comments
	Method	Mixed models repeated measurement (MMRM)
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.74
	Confidence Interval	(2-Sided) 95% 1.33 to 5.62
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg/placebo

5. Secondary Outcome

Title	Proportion of Subjects Losing 4% or More of Baseline Body Weight
Description	The estimated mean percentage of subjects losing 4% or more of baseline body weight at week 16 is presented. The endpoint was evaluated for treatment policy estimand (in-trial data).
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Number [percentage of participants]	78.73 55.4%	52.70 37.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Treatment policy estimand. Week 16 responders were analysed using a logistic regression model with treatment, BMI groups, and sex as factors and baseline body weight as covariate. Missing values are considered as non-responders.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.32
	Confidence Interval	(2-Sided) 95% 1.93 to 5.72
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg/placebo

6. Secondary Outcome

Title	Change in Waist Circumference (cm)
Description	Observed mean change from baseline in waist circumference. The endpoint was evaluated based on in-trial data and on-drug data.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
In-trial observation period	-9.27 (9.22)	-6.91 (8.22)
On-drug observation period	-10.46 (9.22)	-7.24 (8.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach. Week 56 responses were analysed using an analysis of covariance model with treatment, BMI groups, and sex as factors and baseline measurement of endpoint as covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0063
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	treatment difference
	Estimated Value	-2.72
	Confidence Interval	(2-Sided) 95% -4.68 to -0.77
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg - placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups, and sex as factors and baseline measurement of endpoint as covariate, all nested within visit.
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0020
	Comments
	Method	Mixed model repeated measurements (MMRM)
	Comments

Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-3.45
	Confidence Interval	(2-Sided) 95% -5.62 to -1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg - placebo

7. Secondary Outcome

Title	Change in Short Form-36 (SF-36) v2.0 Acute, Physical Functioning Score
Description	SF-36 is a 36-item patient-reported survey of patient health that measures the subject's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in SF-36 physical functioning score is presented. A positive change score indicates an improvement since baseline. The endpoint was evaluated based on in-trial data and on-drug data.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
In-trial observation period	3.55 (6.98)	4.21 (6.85)
On-drug observation period	4.03 (6.49)	4.77 (6.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Treatment policy estimand. Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach. Week 56 responses were analysed using an analysis of covariance model with treatment, BMI groups, and sex as factors and baseline measurement of endpoint as covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8137
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.16
	Confidence Interval	(2-Sided) 95% -1.19 to 1.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg - placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Hypothetical estimand. Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups, and sex as factors and baseline measurement of endpoint as covariate, all nested within visit.
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8053
	Comments
	Method	Mixed model repeated measurements (MMRM)
	Comments

Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.16
	Confidence Interval	(2-Sided) 95% -1.12 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg- placebo

8. Secondary Outcome

Title	Change in IWQoL-Lite for CT, Physical Function Domain (5-items) Score
Description	Observed mean change in Impact of Weight on Quality of Life-Lite for Clinical Trials Version (IWQoL-Lite for CT ) score. IWQoL-Lite for CT (Weight on Quality of Life-Lite for Clinical Trial Version) is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. The endpoint was evaluated based on in-trial data and on-drug data.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
In-trial observation period	13.5 (21.4)	15.5 (23.0)
On-drug observation period	15.2 (21.4)	17.5 (21.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Treatment policy estimand. Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach. Week 56 responses were analysed using an analysis of covariance model with treatment, BMI groups, and sex as factors and baseline measurement of endpoint as covariate.
	Type of Statistical Test	Superiority
	Comments	Superiority was not tested as part of confirmatory testing strategy.

Statistical Test of Hypothesis	p-Value	0.6916
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95% -3.41 to 5.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg - placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Hypothetical estimand. Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups, and sex as factors and baseline measurement of endpoint as covariate, all nested within visit.
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5572
	Comments
	Method	Mixed models repeated measurements (MMRM
	Comments

Method of Estimation	Estimation Parameter	treatment difference
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95% -2.95 to 5.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg - placebo

9. Secondary Outcome

Title	Change in Six Minutes Walking Distance Test (6MWT)
Description	Observed mean change from baseline in 6 minutes walking distance test. The 6MWT is a common test of functional exercise capacity that assesses the distance a subject can walk in 6 minutes. The endpoint was evaluated based on in-trial data and on-drug data.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
In-trial observation period	47 (59)	49 (69)
On-drug observation period	53 (61)	51 (69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Treatment policy estimand. Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach. Week 56 responses were analysed using an analysis of covariance model with treatment, BMI groups, and sex as factors and baseline measurement of endpoint as covariate.
	Type of Statistical Test	Superiority
	Comments	Superiority was not tested as part of confirmatory testing strategy.

Statistical Test of Hypothesis	p-Value	0.6986
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	3.12
	Confidence Interval	(2-Sided) 95% -12.68 to 18.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg - placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Hypothetical estimand. Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups, and sex as factors and baseline measurement of endpoint as covariate, all nested within visit.
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3700
	Comments
	Method	Mixed model repeated measurements (MMRM)
	Comments

Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	7.66
	Confidence Interval	(2-Sided) 95% -9.15 to 24.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg - placebo

10. Secondary Outcome

Title	Change From Baseline in HbA1c (%)
Description	Observed mean change from baseline to week 56 in glycosylated haemoglobin (HbA1c). Results based on FAS in-trial data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [percentage]	-0.2 (0.3)	-0.1 (0.2)

11. Secondary Outcome

Title	Change From Baseline in FPG (mg/dL)
Description	Observed mean change from baseline (week 0) in fasting plasma glucose (FPG). Results based on FAS in-trial data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [mg/dL]	-4.04 (9.59)	-0.28 (11.46)

12. Secondary Outcome

Title	Change From Baseline sBP (mmHg)
Description	Observed mean change in systolic blood pressure from baseline to week 56.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [mmHg]	-2 (14)	-1 (13)

13. Secondary Outcome

Title	Change From Baseline dBP (mmHg)
Description	Observed mean change from baseline (week 0) to week 56 in diastolic blood pressure (dBP). Results based on FAS in-trial data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [mmHg]	-1 (11)	-1 (10)

14. Secondary Outcome

Title	Change From Baseline in Lipids -Total Cholesterol
Description	Observed mean change from baseline (week 0) to week 56 in total cholesterol (TC). Results based on FAS in-trial data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [mmol/L]	-0.01 (0.59)	0.00 (0.77)

15. Secondary Outcome

Title	Change From Baseline in Lipids - LDL Cholesterol
Description	Observed mean change from baseline in low density cholesterol (LDL) from baseline (week 0) to week 56. Results based on FAS in-trial data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [mmol/L]	-0.01 (0.52)	-0.01 (0.64)

16. Secondary Outcome

Title	Change From Baseline in Lipids - HDL Cholesterol
Description	Observed mean change from baseline in high density (HDL) cholesterol from baseline (week 0) to week 56. Results based on FAS in-trial data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [mmol/L]	0.06 (0.19)	0.02 (0.22)

17. Secondary Outcome

Title	Change From Baseline in Lipids - VLDL Cholesterol
Description	Observed mean change from baseline in very low density cholesterol (VLDL) from baseline (week 0) to week 56. Results based on FAS in-trial data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [mmol/L]	-0.06 (0.31)	-0.01 (0.26)

18. Secondary Outcome

Title	Change From Baseline in Lipids - TG
Description	Observed mean change from baseline in triglyceride (TG) from baseline (week 0) to week 56. Results based on FAS in-trial data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [mmol/L]	-0.19 (1.04)	-0.01 (0.58)

19. Secondary Outcome

Title	Change From Baseline in Lipids - FFA
Description	Observed mean change from baseline in free fatty acids (FFA) from baseline (week 0) to week 56. Results based on FAS in-trial data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [mmol/L]	-0.07 (0.28)	-0.06 (0.31)

20. Secondary Outcome

Title	Change in Short Form-36 v2.0 Acute (SF-36) (Subdomains)
Description	SF-36 is a 36-item patient-reported survey of patient health that measures the subject's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in in the sub-domain scores is presented. A positive change score indicates an improvement since baseline. Results are evaluated based on in-trial data.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Bodily Pain	0.67 (7.61)	1.21 (8.88)
General Health Perception	1.89 (6.31)	1.08 (6.62)
Mental Health	-0.93 (7.80)	-0.68 (6.89)
Role Lim Emotion Prob	-1.27 (7.72)	-2.21 (8.59)
Role Lim. Phy Health	2.01 (6.55)	2.11 (7.68)
Social Functioning	1.22 (8.69)	-0.45 (9.61)
Vitality	2.64 (8.99)	2.43 (7.78)

21. Secondary Outcome

Title	Change in Short Form-36 v2.0 Acute (SF-36) (Physical Component Summary (PCS))
Description	Observed mean change from baseline (week 0) to week 56 in short form 36 v2.0 acute domain physical component summary (PCS). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in SF-36 physical component summary (PCS) score is presented. A positive change score indicates an improvement since baseline. The endpoint was evaluated based on in-trial data and on-drug data.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [scores on a scale]	3.41 (6.65)	3.83 (7.22)

22. Secondary Outcome

Title	Change in Short Form-36 v2.0 Acute (SF-36) (Mental Component Summary (MCS)
Description	Observed mean change from baseline (week 0) to week 56 in short form 36 v2.0 acute domain mental component summary (MCS). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in SF-36 mental component summary is presented. A positive change score indicates an improvement since baseline. The endpoint was evaluated based on in-trial data and on-drug data.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [scores on a scale]	-1.22 (8.74)	-2.20 (8.11)

23. Secondary Outcome

Title	Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Pain/Discomfort Domain Score
Description	Observed mean change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT) domain pain and discomfort. IWQoL-Lite for CT (Weight on Quality of Life-Lite for Clinical Trial Version) is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. Results based on FAS in-trial data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [scores on a scale]	10.1 (21.2)	8.6 (23.1)

24. Secondary Outcome

Title	Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Psychosocial Domain Score
Description	Observed mean change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT) psychosocial domain. IWQoL-Lite for CT (Weight on Quality of Life-Lite for Clinical Trial Version) is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. Results based on FAS in-trial data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [score]	13.5 (20.3)	12.4 (21.8)

25. Secondary Outcome

Title	Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT): Total Score
Description	Observed mean change from baseline (week 0) to week 56 in IWQoL-Lite for CT total score. IWQoL-Lite for CT (Weight on Quality of Life-Lite for Clinical Trial Version) is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. Results based on FAS in-trial data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [scores on a scale]	13.2 (18.5)	12.8 (20.7)

26. Secondary Outcome

Title	Change in Weight Related Sign and Symptom (WRSS) Measure, Total Score
Description	Observed mean change from baseline (week 0) to week 56 in WRSS measure, total score. The WRSS measures the presence and bothersome associated with weight-related symptoms. The WRSS questionnaire was not validated until after database lock. Therefore the total score couldn't be calculated and the supportive secondary endpoint "Weight related sign and symptom (WRSS) measure, total score" couldn't be analysed.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [Score on a scale]	NA (NA)	NA (NA)

27. Secondary Outcome

Title	Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 4.3 T-score Points Increase From Baseline in SF-36 Physical Functioning Score
Description	Percentage of subjects who achieved ≥ 4.3 T-score points increase from baseline in SF-36 physical functioning score at week 56 is presented. Results based on FAS in-trial data is presented.
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Number [percentage of participants]	38.7 27.3%	37.9 27.1%

28. Secondary Outcome

Title	Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 3.8 T-score Points Increase From Baseline in SF-36 Physical Component Score
Description	Percentage of subjects who achieved ≥ 3.8 T-score points increase from baseline in SF-36 physical component score at week 56 is presented. Results based on FAS in-trial data is presented.
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Number [Percentage of participants]	43.7 30.8%	41.4 29.6%

29. Secondary Outcome

Title	Subjects Who After 56 Weeks Achieve (Yes/no): ≥ 4.6 T-score Points Increase From Baseline in SF-36 Mental Component Score
Description	Percentage of subjects who achieved ≥ 4.6 T-score points increase from baseline in SF-36 mental component score at week 56 is presented. Results based on FAS in-trial data is presented.
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Number [Percentage of participants]	20.4 14.4%	9.3 6.6%

30. Secondary Outcome

Title	Responder Definition Value for IWQoL-Lite for CT Physical Function Domain (5-items) Score
Description	Responder definition value for IWQoL-Lite for CT physical function domain (5-items) score' was defined as '≥ 20 responder definition value for IWQoL-Lite for CT physical function domain (5-items) score. Percentage of subjects considered IWQoL-Lite for CT physical function domain score responders (increase of ≥20 points) at week 56 is presented. Results based on FAS in-trial data is presented.
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Number [Percentage of participants]	37.3 26.3%	34.3 24.5%

31. Secondary Outcome

Title	Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Trial Product
Description	Adherence to trial product is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to trial product is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [weeks]	49.5 (14.0)	46.8 (16.1)

32. Secondary Outcome

Title	Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet
Description	Adherence to caloric diet is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to caloric diet is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [weeks]	38.4 (16.0)	36.1 (17.3)

33. Secondary Outcome

Title	Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Physical Activity
Description	Adherence to physical activity is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to physical activity is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [weeks]	29.0 (17.1)	30.0 (17.2)

34. Secondary Outcome

Title	Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet and Physical Activity
Description	Adherence to caloric diet and physical activity is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to caloric diet and physical activity is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [weeks]	24.0 (16.0)	24.5 (15.7)

35. Secondary Outcome

Title	Number of Weeks (Completed Calendar Weeks) From Randomisation to Week 56 Adherent to Caloric Diet, Physical Activity and Trial Product
Description	Adherence to caloric diet, physical activity and trial product is assessed regularly at CMS-IBT visits. The number of weeks from randomisation to week 56, adherent to caloric diet, physical activity and trial product is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomised subjects. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [weeks]	22.9 (16.1)	24.0 (15.9)

36. Secondary Outcome

Title	AEs From Randomisation Until and Including the Follow-up Period
Description	Number of adverse events from randomisation to until the end of the post-treatment follow-up period (30 days). Results based on SAS on-drug data is presented.
Time Frame	Week 0 to week 56+30 days

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Number [events]	867	601

37. Secondary Outcome

Title	Change in Physical Examination
Description	Observed change from baseline to week 56 in physical examination are categorised under parameters namely abdomen, gastrointestinal system, cardiovascular system, central and peripheral nervous system, general appearence, head, ears, eyes, nose, throat and neck, lymph node palpation, musculoskeletal system, respiratory system, skin and thyroid gland. The percentage of subjects assessed as normal, abnormal not clinically significant and abnormal clinically significant at baseline and week 56 is presented.
Time Frame	Week 1, week 56

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Abdomen (week -1) Normal	108 76.1%	121 86.4%
Abdomen (week -1) Abnormal, NCS	34 23.9%	19 13.6%
Abdomen (week -1) Abnormal CS	0 0%	0 0%
Abdomen (week 56) Normal	114 80.3%	108 77.1%
Abdomen (week 56) Abnormal, NCS	25 17.6%	12 8.6%
Abdomen (week 56) Abnormal, CS	0 0%	2 1.4%
Gastrointestinal System (week -1) Normal	130 91.5%	129 92.1%
Gastrointestinal System (week -1) Abnormal NCS	12 8.5%	11 7.9%
Gastrointestinal System (week -1) Abnormal CS	0 0%	0 0%
Gastrointestinal System (week 56) Normal	132 93%	116 82.9%
Gastrointestinal System (week 56) Abnormal NCS	7 4.9%	6 4.3%
Gastrointestinal System (week 56) Abnormal CS	0 0%	0 0%
Cardiovascular System (week-1) Normal	136 95.8%	127 90.7%
Cardiovascular System (week-1) Abnormal NCS	6 4.2%	13 9.3%
Cardiovascular System (week-1) Abnormal CS	0 0%	0 0%
Cardiovascular System (week 56) Normal	138 97.2%	116 82.9%
Cardiovascular System (week 56) Abnormal NCS	1 0.7%	5 3.6%
Cardiovascular System (week 56) Abnormal CS	0 0%	1 0.7%
Nervous System (week -1) Normal	135 95.1%	127 90.7%
Nervous System (week -1) Abnormal NCS	5 3.5%	6 4.3%
Nervous System (week -1) Abnormal CS	2 1.4%	7 5%
Nervous System (week 56) Normal	132 93%	112 80%
Nervous System (week 56) Abnormal NCS	6 4.2%	9 6.4%
Nervous System (week 56) Abnormal CS	1 0.7%	1 0.7%
General Appearance (week -1) Normal	118 83.1%	123 87.9%
General Appearance (week -1) Abnormal NCS	24 16.9%	17 12.1%
General Appearance (week -1) Abnormal CS	0 0%	0 0%
General Appearance (week 56) Normal	122 85.9%	112 80%
General Appearance (week 56) Abnormal NCS	17 12%	10 7.1%
General Appearance (week 56) Abnormal CS	0 0%	0 0%
Head, ENTand Neck (week -1) Normal	129 90.8%	128 91.4%
Head, ENTand Neck (week -1) Abnormal NCS	13 9.2%	12 8.6%
Head, ENTand Neck (week -1) Abnormal CS	0 0%	0 0%
Head, ENTand Neck (week 56) Normal	126 88.7%	115 82.1%
Head, ENTand Neck (week 56) Abnormal NCS	13 9.2%	7 5%
Head, ENTand Neck (week 56) Abnormal CS	0 0%	0 0%
Lymph Node Palpation (week -1) Normal	142 100%	140 100%
Lymph Node Palpation (week -1) Abnormal NCS	0 0%	0 0%
Lymph Node Palpation (week -1) Abnormal CS	0 0%	0 0%
Lymph Node Palpation (week 56) Normal	139 97.9%	121 86.4%
Lymph Node Palpation (week 56) Abnormal NCS	0 0%	0 0%
Lymph Node Palpation (week 56) Abnormal CS	0 0%	1 0.7%
Musculoskeletal System (week -1) Normal	131 92.3%	128 91.4%
Musculoskeletal System (week -1) Abnormal NCS	11 7.7%	12 8.6%
Musculoskeletal System (week -1) Abnormal CS	0 0%	0 0%
Musculoskeletal System (week 56) Normal	130 91.5%	112 80%
Musculoskeletal System (week 56) Abnormal NCS	9 6.3%	9 6.4%
Musculoskeletal System (week 56) Abnormal CS	0 0%	1 0.7%
Respiratory System (week -1) Normal	140 98.6%	138 98.6%
Respiratory System (week -1) Abnormal NCS	2 1.4%	2 1.4%
Respiratory System (week -1) Abnormal CS	0 0%	0 0%
Respiratory System (week 56) Normal	138 97.2%	120 85.7%
Respiratory System (week 56) Abnormal NCS	1 0.7%	2 1.4%
Respiratory System (week 56) Abnormal CS	0 0%	0 0%
Skin (week -1) Normal	116 81.7%	114 81.4%
Skin (week -1) Abnormal NCS	26 18.3%	24 17.1%
Skin (week -1) Abnormal CS	1 0.7%	0 0%
Skin (week 56) Normal	117 82.4%	98 70%
Skin (week 56) Abnormal NCS	21 14.8%	24 17.1%
Skin (week 56) Abnormal CS	1 0.7%	0 0%
Thyroid Gland (week -1) Normal	138 97.2%	138 98.6%
Thyroid Gland (week -1) Abnormal NCS	4 2.8%	2 1.4%
Thyroid Gland (week -1) Abnormal CS	0 0%	0 0%
Thyroid Gland (week 56) Normal	136 95.8%	120 85.7%
Thyroid Gland (week 56) Abnormal NCS	3 2.1%	2 1.4%
Thyroid Gland (week 56) Abnormal CS	0 0%	0 0%

38. Secondary Outcome

Title	Change in Resting Pulse
Description	Observed mean change in pulse rate measured at resting position is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [beats/min]	2 (10)	1 (10)

39. Secondary Outcome

Title	Change in ECG
Description	The ECGs were interpreted by the investigator at baseline (week -1) and week 56 and categorised as normal, abnormal NCS or abnormal CS. Number of subjects in each ECG category at baseline and week 56 are presented.
Time Frame	Week -1, week 56

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Normal (week -1)	100 70.4%	91 65%
Abnormal NCS (week -1)	41 28.9%	49 35%
Abnormal CS (week -1)	1 0.7%	0 0%
Normal (week 56)	102 71.8%	81 57.9%
Abnormal NCS (week 56)	36 25.4%	42 30%
Abnormal CS (week 56)	0 0%	1 0.7%

40. Secondary Outcome

Title	Change in Laboratory Measurements: Haematology (Haemoglobin Blood)
Description	Observed mean change from baseline in haematological parameter blood haemoglobin.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [mmol/L]	-0.2 (0.5)	-0.1 (0.6)

41. Secondary Outcome

Title	Change in Laboratory Measurements: Haematology (Haematocrit Blood)
Description	Observed mean change from baseline in haematological parameter blood haematocrit. Haematocrit is presented as the percentage of red blood cells in total blood. Results based on SAS on-drug data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [percentage of red blood cells]	-1.5 (2.3)	-0.9 (2.6)

42. Secondary Outcome

Title	Change in Laboratory Measurements: Haematology (Erythrocytes)
Description	Observed mean change from baseline in haematological parameter - erythrocytes.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [10^12 cells/L]	-0.11 (0.25)	-0.08 (0.25)

43. Secondary Outcome

Title	Change in Laboratory Measurements: Haematology (Thrombocytes and Leukocytes)
Description	Observed mean change from baseline in haematological parameters - thrombocytss and leukocytes.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Thrombocytes	4 (30)	0 (36)
Leukocytes	-0.14 (1.53)	-0.11 (1.20)

44. Secondary Outcome

Title	Change in Laboratory Measurements: Biochemistry (Albumin)
Description	Observed mean change from baseline in biochemical parameter - albumin. Results based on SAS on-drug data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [g/L]	-0.1 (0.2)	-0.1 (0.2)

45. Secondary Outcome

Title	Change in Laboratory Measurements: Biochemistry (Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase)
Description	Observed mean change from baseline in biochemical parameters - alkaline phosphatase, alanine aminotransferase, amylase, aspartate aminotransferase and lipase. Results based on SAS on-drug data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Alkaline Phosphatase	-2 (12)	-1 (13)
Alanine Aminotransferase	-5 (14)	-4 (16)
Amylase	4 (10)	1 (13)
Aspartate aminotransferase	-3 (10)	-2 (12)
Lipase	7 (18)	2 (22)

46. Secondary Outcome

Title	Change in Laboratory Measurements: Biochemistry (Bilirubin and Creatinine)
Description	Observed mean change from baseline in biochemical parameters - bilirubin and creatinine. Results based on SAS on-drug data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Bilirubin	1.1 (3.2)	1.0 (3.2)
Creatinine	-1.8 (7.9)	-1.4 (6.1)

47. Secondary Outcome

Title	Change in Laboratory Measurements: Biochemistry (Total Calcium, Pottassium, Sodium and Urea)
Description	Observed mean change from baseline in biochemical parameters - total calcium, pottassium, sodium and urea. Results based on SAS on-drug data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Total Calcium	0.01 (0.10)	0.01 (0.09)
Potassium	-0.0 (0.5)	-0.0 (0.4)
Sodium	-0.0 (2)	-0 (2)
Urea	0.0 (1.2)	0.2 (1.2)

48. Secondary Outcome

Title	Change in Laboratory Measurements: Biochemistry (C-reactive Protein and Uric Acid)
Description	Observed mean change from baseline in biochemical parameters - high sensitive c-reactive protein and uric acid. Results based on SAS on-drug data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
High sensitive c-reactive protein	-2.51 (4.67)	-0.85 (8.96)
Uric acid	-0.6 (0.9)	-0.3 (0.9)

49. Secondary Outcome

Title	Change in Laboratory Measurements: Biochemistry (Glomerular Filtration Rate, Serum)
Description	Observed mean change from baseline in biochemical parameters - estimated glomerular filtration rate. Serum GFR is estimated using MDRD formula . Results based on SAS on-drug data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [mL/min/1.73m^2]	2 (11)	2 (9)

50. Secondary Outcome

Title	Change in Laboratory Measurements: Biochemistry (Calcitonin)
Description	Observed mean change from baseline in biochemical parameter - calcitonin. Results based on SAS on-drug data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [ng/L]	0.2 (0.8)	0.1 (0.8)

51. Secondary Outcome

Title	Change in Laboratory Measurements: Biochemistry (Thyroid Stimulating Hormone)
Description	Observed mean change from baseline in biochemical parameters - thyroid stimulating hormone. Results based on SAS on-drug data is presented.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description
Safety analysis set included all randomised subjects exposed to at least one dose of trial drug. "Number analysed"=subjects with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.	Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
Measure Participants	142	140
Mean (Standard Deviation) [mIU/L]	-0.2313 (1.0366)	0.2685 (3.6814)

Adverse Events

	Lira 3.0 mg		Placebo
Time Frame	From the date of first dose of trial product (week 0) to end of treatment (week 56) + post treatment follow-up of 30 days.
Adverse Event Reporting Description	Evaluation of safety was based on safety analysis set (SAS) which comprised of all randomised subjects who received at least one dose of trial product. AEs with onset during the on-drug observation period (the period when subjects were exposed to trial product) were considered treatment-emergent.

Arm/Group Title	Lira 3.0 mg		Placebo
Arm/Group Description	Subjects received liraglutide 3.0 mg once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until they reached a maintenance dose of 3.0 mg after 4 weeks. The treatment period was 56 weeks. Subjects were also on CMS-IBT during the trial.		Subjects received matching placebo once daily by subcutaneous injection (in the abdomen, thigh or upper arm) irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. Subjects remained on a stable dose of placebo for 56 weeks. Subjects were also on CMS-IBT during the trial.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/142 (0%)		0/140 (0%)
Serious Adverse Events
	Lira 3.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/142 (4.2%)		2/140 (1.4%)
Gastrointestinal disorders
Colitis	1/142 (0.7%)	1	0/140 (0%)	0
Hepatobiliary disorders
Cholecystitis acute	1/142 (0.7%)	1	0/140 (0%)	0
Injury, poisoning and procedural complications
Ankle fracture	0/142 (0%)	0	1/140 (0.7%)	1
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/142 (0.7%)	2	0/140 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer	1/142 (0.7%)	1	0/140 (0%)	0
Nervous system disorders
Headache	1/142 (0.7%)	1	0/140 (0%)	0
Hydrocephalus	0/142 (0%)	0	1/140 (0.7%)	1
Reproductive system and breast disorders
Ovarian cyst	1/142 (0.7%)	1	0/140 (0%)	0
Other (Not Including Serious) Adverse Events
	Lira 3.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	124/142 (87.3%)		101/140 (72.1%)
Gastrointestinal disorders
Abdominal discomfort	8/142 (5.6%)	9	4/140 (2.9%)	4
Constipation	43/142 (30.3%)	57	26/140 (18.6%)	34
Diarrhoea	31/142 (21.8%)	47	23/140 (16.4%)	26
Dyspepsia	8/142 (5.6%)	13	3/140 (2.1%)	3
Nausea	68/142 (47.9%)	102	25/140 (17.9%)	33
Vomiting	33/142 (23.2%)	47	7/140 (5%)	7
General disorders
Fatigue	13/142 (9.2%)	15	5/140 (3.6%)	5
Infections and infestations
Gastroenteritis viral	3/142 (2.1%)	5	9/140 (6.4%)	9
Influenza	5/142 (3.5%)	5	13/140 (9.3%)	13
Nasopharyngitis	13/142 (9.2%)	17	9/140 (6.4%)	13
Sinusitis	9/142 (6.3%)	10	18/140 (12.9%)	20
Upper respiratory tract infection	32/142 (22.5%)	38	15/140 (10.7%)	17
Urinary tract infection	8/142 (5.6%)	15	3/140 (2.1%)	3
Injury, poisoning and procedural complications
Ligament sprain	6/142 (4.2%)	6	9/140 (6.4%)	9
Muscle strain	3/142 (2.1%)	3	7/140 (5%)	8
Musculoskeletal and connective tissue disorders
Arthralgia	9/142 (6.3%)	10	16/140 (11.4%)	20
Back pain	8/142 (5.6%)	10	13/140 (9.3%)	14
Nervous system disorders
Dizziness	9/142 (6.3%)	10	6/140 (4.3%)	6
Headache	20/142 (14.1%)	23	13/140 (9.3%)	29
Migraine	3/142 (2.1%)	3	9/140 (6.4%)	12
Respiratory, thoracic and mediastinal disorders
Cough	7/142 (4.9%)	7	9/140 (6.4%)	11
Oropharyngeal pain	2/142 (1.4%)	2	7/140 (5%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.

Results Point of Contact

Name/Title	Clinical Reporting Anchor and Disclosure (1452)
Organization	Novo Nordisk A/S
Phone	(+1) 866-867-7178
Email	clinicaltrials@novonordisk.com

Responsible Party:

Novo Nordisk A/S

ClinicalTrials.gov Identifier:

NCT02963935

Other Study ID Numbers:

NN8022-4274
U1111-1177-5059

First Posted:

Nov 15, 2016

Last Update Posted:

Mar 11, 2020

Last Verified:

Feb 1, 2020