Effect of Exenatide in Obese Patients With Accelerated Gastric Emptying

To evaluate the effect of Exenatide 5mcg SQ twice daily for 30-days on gastric emptying,
satiety, satiation and weight loss in obese participants with TCF7L2 "CC compared to TT'
genotype.

Inclusion Criteria:

- Obese subjects with BMI> 30 Kg/m2: Otherwise healthy individuals who are not
currently on treatment for cardiac, pulmonary, gastrointestinal, hepatic, renal,
hematological, neurological, endocrine (other than hyperglycemia not requiring
medical therapy) and unstable psychiatric disease.

- Age: 18-70 years

- Gender: Men or women. Women of childbearing potential will have negative pregnancy
test before initiation of medication.

- Gastric emptying: Accelerated GE T1/2 < 79 minutes or GE 1h>35 %

Exclusion Criteria:

- Type 1 or type 2 diabetes mellitus diagnosed according to American Diabetes
Association criteria

- Unstable heart disease as evidenced by ongoing angina

- Congestive heart failure

- Concomitant use of appetite suppressants (i.e. caffeine based or diethylpropion) or
orlistat (Xenical®)

- Uncontrolled hypertension (Blood pressure greater than 160/90 mmHg)

- use of anti-diabetic drugs including metformin,

- history of nephrolithiasis,

- Recurrent major depression, presence or history of suicidal behaviour or ideation
with intent to act, and current substantial depressive symptoms (Patient Health
Questionnaire [PHQ-9]21 total score ≥10).

- Gastroparesis

- Inflammatory bowel disease or irritable bowel syndrome

- Malignancy treated with chemotherapy within the past 3 years

- History of pancreatitis

- Renal insufficiency (eGFR less than 50 ml/min)

- Concomitant use of MAOI inhibitors (i.e. phenelzine, selegiline), serotonergic
agents, and other centrally acting appetite suppressants

- Significant psychiatric dysfunction based upon screening with the Hospital Anxiety
and Depression Scale [HADS] self-administered alcoholism screening test (SAAST,
substance abuse) and the questionnaire on eating and weight patterns (binge eating
disorders and bulimia). If such a dysfunction is identified by a HADS score ≥11 in
any of the subscales or difficulties with substance or eating disorders, the
participant will be excluded and given a referral letter to his/her primary care
doctor for further appraisal and follow-up.

- Intake of medication that could interfere with the interpretation of the study or
cause drug interaction (i.e. ketoconazole, erythromycin). Specifically, birth control
pill, estrogen replacement therapy, and thyroxine replacement are permissible.