Combinatorial Therapy for Peristent Type 2 Diabetes After Gastric Banding

Liraglutide and Orlistat improve glycemic control by increasing glucagon-like-peptide-1
(GLP-1) response and fat malabsorption, respectively but do not reverse type 2 diabetes.
Roux-en-y gastric bypass (RYGB) surgery reverses type 2 diabetes 84% of the time while the
less invasive, reversible laparoscopic adjustable gastric banding (LAGB) procedure reverses
type 2 diabetes 48% of the time.

Decreased caloric intake occurs after RYGB and LAGB but increased post-prandial GLP-1
response and fat malabsorption only occur after RYGB. Since FDA-approved agents Liraglutide
and Orlistat increase GLP-1 response and fat malabsorption, respectively, it is of
significant clinical interest to determine if addition of Liraglutide and/or Orlistat can
improve type 2 diabetes remission rates in the 52% of patients who have not achieved
diabetes reversal after gastric banding.

Inclusion Criteria:

Subjects will be eligible if they meet the following criteria:

- male or female,

- age 25-70 years,

- BMI 26-65,

- type 2 diabetic,

- weight stable for 3 months,

- status post laparoscopic adjustable gastric banding (LAGB) for at least 1 year,

- hemoglobin a1c 7-10%;

- on any diabetic regimen including insulin except for thiazolidinedione use in the
past 6 months.

Exclusion Criteria:

Subjects will be excluded if they meet any of the following criteria:

- prior history of pancreatitis,

- prior history of gastroparesis,

- glomerular filtration rate (GFR) < 50,

- history of thyroid cancer/multiple endocrine neoplasia/thyroid nodules/medullary
thyroid cancer,

- history of cholelithiasis,

- history of hyperoxaluria or calcium oxalate nephrolithiasis,

- abnormal AST,

- ALT elevation,

- current or past history of liver disease,

- history of Roux-en-y gastric bypass or gastric sleeve or any other bariatric
procedure other than LAGB,

- type 1 diabetes,

- any gastrointestinal disease causing malabsorption (including but not limited to
inflammatory bowel disease, celiac sprue),

- prior history of Orlistat or incretin therapy use in past 3 months,

- unwilling or unable to complete scheduled testing,

- thiazolidinedione use within past 6 months,

- any serious and/or unstable medical, psychiatric, or other condition(s) that prevents
the patient from providing informed consent or complying with the study.

Patients who have had organ transplantation are on chronic anticoagulation, pregnant or
have A1C values > 10% will also be excluded.