Impact of Liraglutide 3.0 on Body Fat Distribution

Obesity has long been recognized as a risk factor for all-cause mortality and morbidity,
including the development of cardiovascular and metabolic diseases such as coronary artery
disease, hypertension, insulin resistance, diabetes, and dyslipidemia. Obesity has recently
been formally defined as a chronic disease characterized by pathophysiological processes that
result in increased adipose tissue mass and can result in increased morbidity and mortality.
Although the health risks associated with obesity are clear, there is an emerging
appreciation that obesity per se, as defined by simple anthropometric measures such as waist
circumference or body mass index (BMI), is neither necessary nor sufficient to promote
cardiometabolic disease and atherosclerotic cardiovascular disease (ASCVD) risk. As a result,
BMI alone is an insufficient marker of risk and may not accurately identify individuals at
elevated risk for ASCVD. There is a pressing need to more accurately phenotype obesity to
identify individuals at elevated risk for ASCVD that may benefit from more intensive
preventive and therapeutic strategies

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 GLP-1 receptor agonists (including liraglutide, exenatide or others as
they become available), 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, clorpromazine, 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 spermacide, condom with spermacide (by male
partner), intrauterine device, sponge, spermacide, Norplant®, Depo-Provera® or oral
contraceptives.