Pilot Study of the Effect of Liraglutide on Weight Loss and Gastric Functions in Obesity

The objective of this study was to compare effects of liraglutide and placebo over 16 weeks
on gastric motor functions, satiation, satiety and weight in obese patients. Subjects were
randomized to liraglutide or placebo. Liraglutide or placebo was escalated by 0.6mg/day each
week for 5 weeks and continued until week 16. At baseline and after 16 weeks' treatment, the
investigators measured weight, gastric emptying of solids (GES), gastric volumes, satiation
(maximum tolerated volume of liquid nutrient drink), and satiety. GES was also measured at 5
weeks.

During the study, the subjects received standardized dietetic and behavioral advice for
weight reduction therapy. All subjects were given a standard text for information and met
with a behavioral psychologist who has expertise in obesity treatment at the baseline visit
and at visits at weeks 4,8, and 12. Additionally, the subjects had brief contact with a
member of the study team every 4 weeks to inquire about their adherence to study protocol,
any difficulties they were experiencing, whether they were reading their text assignments,
and to answer any additional questions.

Inclusion Criteria:

- Overweight and obese adults (≥30 kg/m^2 or ≥27 kg/m^2 with an obesity-related
co-morbidity).

- Subjects residing within 125 miles of Mayo Clinic in Rochester, Minnesota.

- Healthy individuals with no unstable psychiatric disease and not currently on
treatment for cardiac, pulmonary, gastrointestinal, hepatic, renal, hematological,
neurological, or endocrine (other than hyperglycemia type 2 diabetes mellitus on
metformin) disorders.

- Women of childbearing potential will be using an effective form of contraception, and
have negative pregnancy tests within 48 hours of enrolment and before each radiation
exposure.

- Subjects must have the ability to provide informed consent before any trial-related
activities.

Exclusion criteria:

- Weight exceeding 137 kilograms (safety limit of camera for measuring gastric volumes).

- Abdominal surgery other than appendectomy, Caesarian section or tubal ligation.

- Positive history of chronic gastrointestinal diseases, systemic disease that could
affect gastrointestinal motility, or use of medications that may alter
gastrointestinal motility, appetite or absorption, e.g., orlistat.

- Patients with a personal or family history of medullary thyroid carcinoma or Multiple
Endocrine Neoplasia-type 2.

- Patients with a personal history of pancreatitis (acute or chronic)

- Significant untreated psychiatric dysfunction based upon screening with the Hospital
Anxiety and Depression Inventory, a self-administered alcoholism screening test
(AUDIT-C), and the Questionnaire on Eating and Weight Patterns (binge eating disorders
and bulimia). If such a dysfunction is identified by a Hospital Anxiety Depression
(HAD) score >8 or difficulties with substance or eating disorders, the participant
will be excluded and given a referral letter to his/her primary care doctor for
further appraisal and follow-up.

- Intake of medication, whether prescribed or over the counter (except multivitamins),
within 7 days of the study. Exceptions are birth control pill, estrogen replacement
therapy, thyroxin replacement therapy and any medication administered for
co-morbidities as long as they do not alter gastrointestinal motility including
gastric emptying (GE) and gastric accommodation. For example, statins for
hyperlipidemia, diuretics, β-adrenergic blockers,Angiotensin Converting Enzyme (ACE)
inhibitors and angiotensin antagonists for hypertension, and metformin for type 2
diabetes mellitus or prediabetes are permissible. In contrast, resin sequestrants for
hyperlipidemia [which may reduce GE and reduce appetite, α2-adrenergic agonists for
hypertension, or other glucagon-like peptide-1 receptor agonists (GLP-1) receptor
agonists (exenatide) or amylin analogs (pramlintide) are not permissible because they
significantly affect GE and/or gastric accommodation.

- Hypersensitivity to the study medication, liraglutide.