Liraglutide in Obesity and Diabetes: Identification of CNS Targets Using fMRI
Liraglutide in Obesity and Diabetes: Identification of CNS Targets Using fMRI
The main purpose of this study is to help us understand the effects of diabetes medication
 Liraglutide on weight loss and hunger. The investigators have already determined what the
 highest tolerated dose of Liraglutide is through earlier human research studies. Liraglutide
 was approved by the FDA in January 2010 for treatment of diabetes.

 The investigators will also study the following:

 1. The impact of Liraglutide on brain responses to food

 2. It's effect on physiological and mental performance

 3. If its effect on the brain differs among obese and lean diabetic subjects.
This is a randomized, placebo controlled, cross-over, double-blinded study to assess the
 effects of liraglutide on brain activation in areas involved in cognitive control and reward
 during food visualization.

 Study participation will span approximately 1.5-2 months. Subjects will learn to
 self-administer the medication and will have a total of 8 study visits plus one screening
 visit. The visits will include the following tests/procedures:

 1. Vital signs (blood pressure, temperature, heart rate, breathing rate)

 2. Height, weight and other body measurements like waist

 3. Blood tests

 4. Urine pregnancy test (women only)

 5. Electrocardiogram (EKG)

 6. Medical history

 7. Physical exam

 8. Body Composition tests

 9. Study logs to record food intake and blood sugar

 10. functional MRI

 We plan to recruit a total of 24 subjects to be treated with placebo and liraglutide. We
 propose to enroll 12 obese diabetic (type 2) and 12 lean diabetic (type 2) subjects. Equal
 numbers of men and women will be enrolled and the randomization will block for gender.
Inclusion Criteria:

 Subjects will be men and women between the ages of 18 and 65. The following table list
 inclusion criteria for each group (lean diabetic and obese diabetic). Subjects must meet
 either HbA1c or fasting plasma glucose (FPG) criteria.

 Lean diabetic:

 BMI: 18-25 kg/m2 HbA1c: < 8.9% Fasting plasma glucose: <250 mg/dL Other inclusion criteria:
 On dietary modification and/or metformin

 Obese diabetic:

 BMI: >27 kg/m2 HbA1c: < 8.9% Fasting plasma glucose: <250 mg/dL Other inclusion criteria:
 On dietary modification and/or metformin

 Additionally, women participants must use double barrier methods to prevent pregnancy
 (diaphragm with intravaginal spermicide, cervical cap, male or female condom with
 spermicide). If a woman suspects that she has become pregnant at any time or does not use
 one of the contraceptive methods recommended by the investigator, she must notify the study
 staff. If a woman becomes pregnant, she will be withdrawn from the study. The study staff
 will follow the progress of her pregnancy and the birth of her child.

 Exclusion Criteria:

 1. Uncontrolled diabetes (HbA1c>8.9%, or FPG>250 mg/dL)

 2. Women who are breastfeeding, pregnant, or wanting to become pregnant.

 3. Women using IUD

 4. 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.

 5. Moderate (creatinine clearance of 30-59 ml/min) and severe renal impairment
 (creatinine clearance below 30 ml/min) and end-stage renal disease

 6. Moderate, or severe hepatic impairment

 7. Hypersensitivity to the active substance or any of the excipients in liraglutide

 8. History of diabetic ketoacidosis

 9. Congestive heart failure

 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 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 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. Irregular periods, defined as cycle length less than 22 days or more than 40 days.

 37. Any change in smoking status.

 38. Vegetarians- as food images presented will include numerous non-vegetarian items and
 thus will not be appealing as high calorie food items.