The Effect of GLP-1 Receptor Activation on Central Reward and Satiety in Obesity and Diabetes

For all 3 study groups:

1. age 18-70 years.
2. Men and women. For women, only postmenopausal women (as ascertained by serum FSH) will be included in order to avoid variations related to the menstrual cycle.
3. To promote comparability and to overcome the interference of lateralization, only right-handed persons will be included.

For the healthy lean subjects, inclusion criteria will be:

1. body-mass index (BMI) of \<25 kg/m2
2. stable bodyweight (\<5% reported change during the previous 3 months)
3. Normal fasting and 2-h postload glucose as ascertained during a 75-g oral glucose tolerance test (OGTT)

For the normoglycemic obese individuals, inclusion criteria will be:

1. body-mass index (BMI) ≥30 kg/m2
2. stable bodyweight (\<5% reported change during the previous 3 months)
3. Normal fasting and 2-h postload glucose as ascertained during a 75-g oral glucose tolerance test (OGTT)

For the obese T2DM individuals, inclusion criteria will be:

1. Diagnosed with T2DM (20) > 3 months prior to screening
2. BMI ≥30 kg/m2
3. HbA1c 6.2-8.5%
4. Treatment with metformin at a stable dose for at least 3 months.

Exclusion Criteria:

In the obese T2DM patients, no blood glucose- and weight lowering agents will be allowed within 3 months before screening except for metformin. The normoglycemic lean and obese individuals will not be allowed to take blood glucose-lowering agents at any time before and during the study.

For all individuals, exclusion criteria will be:

1. congestive heart failure (NYHA II-IV)
2. chronic renal failure (glomerular filtration rate \< 60 mL/min/1.73m2 per Modification of Diet in Renal Disease (MDRD)) or serious liver impairment
3. a history of gastrointestinal disorders, including gastroparesis, pancreatitis and cholelithiasis
4. neurological illness
5. malignancy
6. pregnancy or breast feeding
7. implantable devices
8. substance abuse
9. addiction
10. contra-indication for MRI, such as claustrophobia or pacemaker
11. any psychiatric illness, including eating disorders and depression
12. hypersensitivity to the active substance or to any of the excipients
13. chronic use of glucocorticoids or centrally acting drugs within 2 weeks immediately prior to screening
14. use of cytostatic or immuno-modulatory agents
15. participation in other studies
16. individuals who have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
17. individuals who are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted
18. individuals who have previously completed or withdrawn from this study or any other study investigating GLP-1 receptor agonist or dipeptidyl peptidase (DPP)-4 within 6 months
19. individuals, who in the opinion of the investigator, are unsuitable in any other way to participate in this study
20. individuals who are employed by Amylin Pharmaceutical Inc. or Eli Lilly \& company (that is, employees, temporary contract workers, or designees responsible for conducting the study). Immediate family of Amylin or Lilly employees may participate in sponsored clinical trials, but are not permitted to participate at an Amylin or Lilly facility. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted
21. poor commandment of the Dutch language or any (mental) disorder that precludes full understanding the purpose, instruction and hence participation in the study.