Saxenda: Underlying Mechanisms and Clinical Outcomes

The purpose of this protocol is to investigate the effect of treatment with the study drug Liraglutide, a GLP-1 receptor agonist, on centers of the brain that control appetite and food intake.

The effect of treatment with the study drug Liraglutide, a recently discovered GLP-1 receptor agonist, on centers of the brain that control appetite and food intake will be studied in detail.

Eligibility Criteria:
Inclusion Criteria:

* Obese: BMI\> 30 kg/m2 or \>27 kg/m2 with comorbidities (including but not limited to insulin resistance, hypertension, dyslipidemia, cardiovascular disease, stroke, sleep apnea, gallbladder disease, hyperuricemia and gout, and osteoarthritis).

Exclusion Criteria:

1. Women who are breastfeeding, pregnant, or wanting to become pregnant.
2. Women using metal IUD
3. Any change in the dosage of hormonal contraceptive medications (birth control pills, implanon). Subjects should remain on same medication/ same dose during the time of the entire study.
4. Moderate (creatinine clearance of 30-59 ml/min) and severe renal impairment (creatinine clearance below 30 ml/min) and end-stage renal disease
5. Moderate, or severe hepatic impairment
6. Hypersensitivity to the active substance or any of the excipients in liraglutide
7. History of diabetic ketoacidosis
8. Congestive heart failure
9. EKG abnormalities (as listed above)
10. Inflammatory conditions like inflammatory bowel disease, Rheumatoid arthritis etc
11. Gastroparesis
12. Pancreatitis
13. Gallstones- as they may cause increased risk of pancreatitis
14. Alcohol consumption- the maximum quantity for men is 140g-210g per week. For women, the range is 84g-140g per week or drinking as consuming no more than two drinks a day for men and one for women. Alcohol can cause increased risk of pancreatitis and hypoglycemia.
15. Untreated thyroid disease like hypothyroidism or hyperthyroidism
16. Subjects taking the following medications: warfarin, steroids (inhaled or systemic due to reduced hypoglycemic effect), and subjects on other hormones (LHRH analogs etc).
17. Subjects on any oral anti-diabetic agent except metformin
18. Personal or family history of MEN II or medullary thyroid cancer
19. Subjects with any type of bioimplant activated by mechanical, electronic, or magnetic means (e.g. cochlear implants, pacemakers, neuron or biostimulators, electronic infusion pumps, etc.)
20. Subjects with any type of metallic implant that could potentially be displaced or damaged during MRI, such as aneurysm clips, metallic skull plates, surgical implants etc. or metal containing tattoos
21. Anxiety of small spaces and/or claustrophobia
22. Uncontrolled cardiac impairment, circulatory impairment, or inability to perspire (poor thermoregulatory function)
23. Significant sensory or motor impairment
24. Epilepsy, particularly photo-sensitive epilepsy, which may place the individual at a higher risk for adverse events during fMRI scanning with visual stimulation
25. Subjects with neurological or psychological problems which may interfere with or complicate testing (e.g. presence of titubation)
26. Body weight above the limitation of the MRI scanning table (330lbs/150 Kg) or body dimensions that could difficult the performance of the scan.
27. Subjects who cannot adhere to the experimental protocol for any reason
28. Anemia with Hgb less than 10
29. Uncontrolled infectious diseases (e.g. HIV, hepatitis, chronic infections etc)
30. Any uncontrolled endocrine condition, e.g Cushing's, Acromegaly, etc
31. Any cancers or lymphoma
32. Eating disorders like anorexia, bulimia
33. Severe hypertriglyceridemia (triglycerides \>500 mg/dl)
34. Weight loss surgery or gastrectomy
35. Any changes in medications that affect brain function, e.g. anti-depressants, anti-psychotics, anti-anxiety, anti-seizure medications, antihypertensives etc (subjects should remain on same medication/ same dose during the time of the entire study).
36. Vegetarians- as food images presented will include numerous non-vegetarian items and thus will not be appealing as high calorie food items.
37. Suicidality, as measured by the MSSI at screening visit.