Comparison of Liraglutide Versus Placebo in Weight Loss Maintenance in Obese Subjects: SCALE - Maintenance

• Mean Percentage Change in Fasting Body Weight From Baseline [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
• Percentage of Subjects Who Maintained Their run-in Fasting Weight Loss From Week 0 [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Subjects who had a weight regain less than or equal to 0.5% of weight from Week 0 were regarded as maintenance of run-in fasting weight loss. Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
• Percentage of Subjects Who Lost More Than or Equal to 5% of Fasting Body Weight From Week 0 [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.

• Mean percentage change in fasting body weight from trial start [ Time Frame: across approx. 78 weeks ] [ Designated as safety issue: No ]
• Percentage of subjects who maintain their run-in fasting weight loss after 52 weeks of treatment [ Time Frame: across approx. 78 weeks ] [ Designated as safety issue: No ]

• Percentage of Subjects Who Lost More Than 10% of Fasting Body Weight From Week 0 [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
• Percentage of Subjects With Weight Regain (Fasting) More Than or Equal to 5% From Week 0 [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
• Percentage of Subjects With Weight Regain (Fasting) More Than or Equal to 10% From Week 0 [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
• Percentage of Subjects With Greater Than 50% of Fasting run-in Weight Loss Maintained From Week 0 [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
• Percentage of Subjects With Greater Than 75% of Fasting run-in Weight Loss Maintained From Week 0 [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
• Change From Baseline in Fasting Weight [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
• Change From Baseline in Fasting Weight for Subjects Completing the Main Trial Period and Entering the Follow-up Period [ Time Frame: Week 0, week 68 ] [ Designated as safety issue: No ]
  Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
• Change From Baseline in Blood Pressure [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
• Change From Baseline in Pulse [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
• Change From Baseline in Fasting Lipid Profile: Triglycerides [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Subjects were tested having fasted (consumed only water) since midnight the night before the visit.
• Change From Baseline in Fasting Lipid Profile: Low Density Lipoprotein (LDL) Cholesterol [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Subjects were tested having fasted (consumed only water) since midnight the night before the visit.
• Change From Baseline in Fasting Lipid Profile: Total Cholesterol [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Subjects were tested having fasted (consumed only water) since midnight the night before the visit.
• Change From Baseline in Cardiovascular Biomarker: High Sensitivity C-reactive Protein (hsCRP) [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
• Percentage of Subjects Meeting Metabolic Syndrome Criteria: ATP (Adult Treatment Panel) III at Week 56 [ Time Frame: Week 56 ] [ Designated as safety issue: No ]
  Metabolic syndrome status required at least 3 of 5 criteria met: Waist circumference (men ≥102cm, women ≥88cm); Triglycerides >1.7mmol/L; High density lipoprotein cholesterol (men <0.9mmol/L, women <1.1mmol/L) or on drug therapy; Blood pressure ≥130mmHg systolic or ≥85mmHg diastolic or on drug therapy; Fasting glucose ≥5.5mmol/L or on drug therapy.
• Change From Baseline in Waist Circumference [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
• Change From Baseline in Body Mass Index (BMI) [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
• Change From Baseline in Glycaemic Control Parameter: HOMA-B (Homeostasis Model Assessment - Beta Cell Function) [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Change in beta-cell function percent values from Week 0 (X%) to Week 56 (Y%) was calculated [X% - Y%]. Beta-cell function was derived from fasting plasma glucose readings in blood samples using the HOMA method, which is based on the assumption that normal-weight subjects without diabetes aged <35 years have median beta-cell function indexed at 100%.
• Change From Baseline in Glycaemic Control Parameter: HOMA-IR (Homeostasis Model Assessment - Insulin Resistance) [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Change in insulin resistance values from Week 0 (X) to Week 56 (Y) was calculated [X - Y]. Insulin resistance was derived from fasting serum insulin levels in blood samples using the HOMA method, which is based on the assumption that normal-weight subjects without diabetes aged <35 years have median insulin resistance indexed at 1.00.
• Change From Baseline in Glycaemic Control Parameter: Fasting Plasma Glucose (FPG) [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Subjects were tested having fasted (consumed only water) since midnight the night before the visit.
• Change From Baseline in Glycaemic Control Parameter: Fasting Serum Insulin [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Subjects were tested having fasted (consumed only water) since midnight the night before the visit.
• Change From Baseline in Glycaemic Control Parameter: HbA1c (Glycosylated Haemoglobin) [ Time Frame: Week 0, week 56 ] [ Designated as safety issue: No ]
  Change in HbA1c percent values from Week 0 (X%) to Week 56 (Y%) was calculated [X% - Y%].
• Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications) [ Time Frame: Week 0 and week 56 ] [ Designated as safety issue: No ]
  Number of subjects using concomitant medications at Week 0 and Week 56, respectively
• Binge Eating Scale Scores by Week and Severity [ Time Frame: Week 0, week 50 and week 57 ] [ Designated as safety issue: No ]
  Binge Eating Scale (BES) scores are based on responses to the Binge Eating Scale Questionnaire, a 16-item self-reporting diagnostic tool scaled 0-46 (Non-binging: 0-17; Moderate: 17-26; Severe: 27-46)

• Percentage of subjects with weight loss of between 5% and 10% of fasting body weight at 52 weeks vs. trial start [ Time Frame: across approx. 78 weeks ] [ Designated as safety issue: No ]
• Percentage of subjects with weight regain (fasting) from trial start of between 5% and 10% [ Time Frame: across approx. 78 weeks ] [ Designated as safety issue: No ]
• Percentage of subjects with greater than 50% and greater than 75% of fasting run-in weight loss maintained at week 52 [ Time Frame: across approx. 78 weeks ] [ Designated as safety issue: No ]
• Change in fasting weight for subjects completing the main trial and entering the follow-up period [ Time Frame: From baseline to end-of-treatment and to end of 12 week follow-up period ] [ Designated as safety issue: No ]
• Change in cardiovascular risk factors [ Time Frame: across approx. 78 weeks ] [ Designated as safety issue: Yes ]
• Vital signs (blood pressure and pulse) [ Time Frame: across approx. 78 weeks ] [ Designated as safety issue: Yes ]
• Fasting lipid profile [ Time Frame: across approx. 78 weeks ] [ Designated as safety issue: No ]
• Cardiovascular biomarkers [ Time Frame: across approx. 78 weeks ] [ Designated as safety issue: No ]
• Metabolic syndrome status (ATP III) [ Time Frame: across approx. 78 weeks ] [ Designated as safety issue: No ]
• Waist circumference and BMI (Body Mass Index) [ Time Frame: across approx. 78 weeks ] [ Designated as safety issue: No ]
• Change in parameters of glycaemic control (HOMA, FPG, fasting serum insulin, and glycosylated haemoglobin (HbA1c)) [ Time Frame: across approx. 78 weeks ] [ Designated as safety issue: No ]
• Change in concomitant medications: lowering of dose or discontinuation of anti-hypertensive medications and lipid lowering medications [ Time Frame: across approx. 78 weeks ] [ Designated as safety issue: No ]
• Binge eating assessment [ Time Frame: across approx. 78 weeks ] [ Designated as safety issue: No ]

This trial is conducted in North America. The aim of this clinical trial is to evaluate the potential of liraglutide to maintain long term weight loss in obese non-diabetic subjects, as well as in overweight subjects who have medical problems such as hypertension (high blood pressure) or dyslipidaemia (an abnormal amount of lipids in the blood).

Trial has following trial periods: A 12-week run-in period (from week -12 to week 0) followed by a 56-week main trial period (weeks 0-56) and a 12-week follow-up period (weeks 56-68).

• Metabolism and Nutrition Disorder
• Obesity

• Drug: liraglutide
  Liraglutide 3.0 mg per day administered in a 6.0 mg/mL, 3 mL FlexPen® for subcutaneous (under the skin) injection, once daily
• Drug: placebo
  Liraglutide placebo 3 mL FlexPen® for subcutaneous (under the skin) injection, once daily

• Experimental: Lira 3.0 mg
  A 12-week run-in period where screened subjects were treated with a low calorie diet. Randomised subjects (those who lost more than or equal to 5% of screening body weight) were treated with liraglutide 3.0 mg, once daily, injected subcutaneously and instructed to follow a standard energy-restricted diet in the 56-week main trial period. Subjects discontinued treatment in the 12-week follow-up period. The starting dose of liraglutide was 0.6 mg, with weekly increments of 0.6 mg every 7 days until the target dose of 3.0 mg was reached
  Intervention: Drug: liraglutide
• Placebo Comparator: Placebo
  A 12-week run-in period where screened subjects were treated with a low calorie diet. Randomised subjects (those who lost more than or equal to 5% of screening body weight) were treated with liraglutide placebo, once daily, injected subcutaneously for 56 weeks and instructed to follow a standard energy-restricted diet in the 56-week main trial period. Subjects discontinued treatment in the 12-week follow-up period
  Intervention: Drug: placebo

Inclusion Criteria:

• Body Mass Index (BMI) of either 30 kg/m^2 or more or BMI of less than 30 kg/m^2 to 27 kg/m^2 with presence of co-morbidities
• Stable body weight during the previous 3 months (less than 5 kg self-reported weight change)
• Previously undergone dietary weight loss and was not able to maintain reduced weight

Exclusion Criteria:

• Diagnosis of type 1 or type 2 diabetes
• Previous treatment with GLP-1 (glucagon-like peptide-1) receptor agonists (including liraglutide or exenatide), within the last 3 months
• Visit 1 thryoid stimulating hormone (TSH) outside of the range of 0.4-6.0 mIU/L
• History of chronic pancreatitis or idiopathic acute pancreatitis
• Obesity induced by other endocrinologic disorders (e.g., Cushing Syndrome)
• Current or history of treatment with medications that may cause significant weight gain for at least 3 months before this trial
• Current participation in an organized diet reduction program (or within the last 3 months)
• Currently using or have used within three months before this trial: pramlintide, sibutramine, orlistat, zonisamide, topiramate, phenteremine, or metformin
• Previous surgical treatment for obesity (excluding liposuction if performed more than one year before trial entry)
• History of major depressive disorder or a PHQ-9 (Patient Health Questionnaire-9) score of more than 15 within the last 2 years or history of other severe psychiatric disorders or diagnosis of an eating disorder
• Subjects with a lifetime history of a suicide attempt or history of any suicidal behavior within the past month before entry into the trial