The purpose of this study is to find out how exenatide causes weight loss. Specifically, the study is assessing how exenatide may change how people take in energy (energy intake), as well as how it may effect how people use energy (energy expenditure).

The bioenergetics study is looking at how and why the diabetes drug exenatide causes people to lose weight.Bioenergetics is the study of how your body burns calories.

Adults 18-65 who do not have diabetes and have a body mass index (BMI) between 30 and 40 may be eligible. Women who could get pregnant must be on birth control during the study and women who are pregnant cannot participate in the study.

Subjects will take exenatide for 12 weeks. There are 6 study visits in the Univ. Wisconsin Hospital General Clinical Research Center. Visits range from 1 to 6 hours and include blood and urine tests, resting metabolic rate testing over a four hour period, physical exam, ECG, and a be bone mineral density testing at another clinic during 2 clinic visits of the study.

All study procedures and testing are free of charge.

Inclusion Criteria:

• 18-65 years of age
• BMI between 30 and 40 kg/m2
• Women with a negative pregnancy test at baseline, who are sterile, using contraceptives or in a committed relationship with someone who is sterile or using contraception
• Absence of weight change greater than 3 kg in the previous 6 months

Exclusion Criteria:

• Women who are pregnant or lactating
• Current or recent (6 months) enrollment in a commercial or self prescribed weight loss or exercise program
• Use of weight loss medication
• A history of metabolic disease i.e. renal, endocrine, hepatic or gastrointestinal disease that would impact the outcome of the study
• Presence of medical conditions that are known to affect energy expenditure (i.e. hyperthyroidism, rheumatoid arthritis, AIDS among others)
• History of hypoglycemia
• A history of psychiatric or eating disorder
• Abnormal EKG
• Previous history of pancreatitis
• Previous history of gastroparesis or GI motility disorder
• Use of medications that can affect GI motility
• History of organ transplantation
• Other comorbid conditions which may preclude the subject's ability to complete the study
• Use of a carbonic anhydrase inhibitor such as acetazolamide

3 months

periodic self-report

study was limited by the number of subjects who did not complete the study as a result of nausea. The nausea was short-lived and mild in all subjects that completed the study.