Impact of Liraglutide 3.0 on Body Fat Distribution
Condition: Obesity, Visceral; Cardiovascular Diseases; Fat Disorder
MeSH terms: Cardiovascular Diseases; Obesity, Abdominal
Intervention: Liraglutide; Placebo
Intervention description: Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.; Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.
Intervention MeSH terms: Liraglutide
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 235.0
Sex: All
Minimum age: 35 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Obesity; Visceral; Cardiovascular Disease; Fat

Summary:

      This study is a clinical study to investigate the efficacy of liraglutide compared to placebo
      in reducing visceral adiposity measured by MRI in overweight or obese subjects at high risk
      for cardiovascular disease after 40 weeks on-treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 35 years

          -  Able to provide informed consent

          -  BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with metabolic syndrome

          -  Metabolic syndrome is defined as at least three of the following:3

               1. waist circumference > 102 cm (40 in) in men and 88 cm (35 in) in women

               2. triglycerides > 150 mg/dL or on treatment for hypertriglyceridemia

               3. HDL cholesterol < 40 mg/dL in men and < 50 mg/dL in women

               4. blood pressure > 130/85 mmHg or on treatment for hypertension

               5. fasting glucose > 100 mg/dL

        Exclusion Criteria:

          -  Treatment with Glucagon-like peptide-1 (GLP-1) receptor agonists (including
             liraglutide, exenatide or others as they become available), dipeptidyl peptidase 4
             (DPP-4) inhibitors or insulin within the last 3 months.

          -  Receipt of any anti-obesity drug or supplement within 1 month prior to screening for
             this trial.

          -  Self-reported or clinically documented history of significant fluctuations (>5%
             change) in weight within 3 months prior to screening for this trial.

          -  History of diabetes mellitus (type 1 or 2) or on treatment with anti-diabetes
             medication.

          -  History of chronic pancreatitis or idiopathic acute pancreatitis (current or prior
             history).

          -  History of gallbladder disease (cholelithiasis or cholecystitis).

          -  Chronic kidney disease stage III or greater (eGFR<60 mL/min).

          -  Obesity induced by other endocrinologic disorders (e.g. Cushing Syndrome).

          -  Current or history of treatment with medications that may cause significant weight
             gain, within 1 month prior to screening for this trial, including systemic
             corticosteroids (except for a short course of treatment, i.e., 7- 10 days), tri-cyclic
             antidepressants, atypical antipsychotic and mood stabilizers (e.g., imipramine,
             amitryptiline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine,
             clozapine, olanzapine, valproic acid and its derivatives, and lithium).

          -  Diet attempts using herbal supplements or over-the-counter medications within 1 month
             prior to screening for this trial.

          -  Current participation in an organized weight reduction program or within the last 1
             month prior to screening for this trial.

          -  Participation in a clinical trial within the last 3 months prior to screening for this
             trial.

          -  Familial or personal history of multiple endocrine neoplasia type 2 or familial
             medullary thyroid carcinoma.

          -  Personal history of non-familial medullary thyroid carcinoma.

          -  History of Major Depressive Disorder within the last 2 years.

          -  History of other severe psychiatric disorders, e.g., schizophrenia, bipolar disorder.

          -  Any lifetime history of a suicide attempt.

          -  A history of any suicidal behavior in the last month prior to randomization.

          -  Surgery scheduled for the trial duration period, except for minor surgical procedures,
             at the discretion of the Investigator.

          -  Known or suspected hypersensitivity to trial product(s) or related product(s).

          -  Known or suspected abuse of alcohol or narcotics.

          -  Language barrier, mental incapacity, unwillingness or inability to understand.

          -  Females of childbearing potential who are pregnant, breast-feeding or intend to become
             pregnant or are not using adequate contraceptive methods. These include abstinence and
             the following methods: diaphragm with spermicide, condom with spermicide (by male
             partner), intrauterine device, sponge, spermicide, Norplant®, Depo-Provera® or oral
             contraceptives.