Saxenda: Underlying Mechanisms and Clinical Outcomes

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.

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

• Women who are breastfeeding, pregnant, or wanting to become pregnant.
• Women using metal IUD
• 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.
• Moderate (creatinine clearance of 30-59 ml/min) and severe renal impairment (creatinine clearance below 30 ml/min) and end-stage renal disease
• Moderate, or severe hepatic impairment
• Hypersensitivity to the active substance or any of the excipients in liraglutide
• History of diabetic ketoacidosis
• Congestive heart failure
• EKG abnormalities (as listed above)
• Inflammatory conditions like inflammatory bowel disease, Rheumatoid arthritis etc
• Gastroparesis
• Pancreatitis
• Gallstones- as they may cause increased risk of pancreatitis
• 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.
• Untreated thyroid disease like hypothyroidism or hyperthyroidism
• Subjects taking the following medications: warfarin, steroids (inhaled or systemic due to reduced hypoglycemic effect), and subjects on other hormones (LHRH analogs etc).
• Subjects on any oral anti-diabetic agent except metformin
• Personal or family history of MEN II or medullary thyroid cancer
• 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.)
• 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
• Anxiety of small spaces and/or claustrophobia
• Uncontrolled cardiac impairment, circulatory impairment, or inability to perspire (poor thermoregulatory function)
• Significant sensory or motor impairment
• Epilepsy, particularly photo-sensitive epilepsy, which may place the individual at a higher risk for adverse events during fMRI scanning with visual stimulation
• Subjects with neurological or psychological problems which may interfere with or complicate testing (e.g. presence of titubation)
• Body weight above the limitation of the MRI scanning table (330lbs/150 Kg) or body dimensions that could difficult the performance of the scan.
• Subjects who cannot adhere to the experimental protocol for any reason
• Anemia with Hgb less than 10
• Uncontrolled infectious diseases (e.g. HIV, hepatitis, chronic infections etc)
• Any uncontrolled endocrine condition, e.g Cushing's, Acromegaly, etc
• Any cancers or lymphoma
• Eating disorders like anorexia, bulimia
• Severe hypertriglyceridemia (triglycerides >500 mg/dl)
• Weight loss surgery or gastrectomy
• 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).
• Vegetarians- as food images presented will include numerous non-vegetarian items and thus will not be appealing as high calorie food items.
• Suicidality, as measured by the MSSI at screening visit.