Combinatorial Therapy for Peristent Type 2 Diabetes After Gastric Banding

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether addition of 1 or 2 medicines after gastric banding can improve remission of type 2 diabetes.

Detailed Description
-----------------
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.

Official Title
-----------------
LIRAGLUTIDE AND ORLISTAT TREATMENT FOR PERSISTENT TYPE 2 DIABETES AFTER GASTRIC BANDING: A PILOT STUDY

Conditions
-----------------
Type 2 Diabetes, Gastric Banding

Intervention / Treatment
-----------------
* Drug: Liraglutide
* Drug: Orlistat
* Drug: Liraglutide + Orlistat


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Liraglutide only<br> | Drug: Liraglutide<br>* Liraglutide will be started at 0.6 mg injected subcutaneously daily for 1 week and then increased as tolerated to 1.2 mg and then a 1.8 mg daily.<br>|
| Active Comparator: Orlistat only<br> | Drug: Orlistat<br>* Orlistat will be started initially at a dose of 60 mg taken with the evening meal. Additional doses will be added at breakfast or lunch every 1-2 weeks as tolerated. The patient will be advised to skip drug dosing if little or no fat is contained in the meal. Target dose will 60 mg three times a day and the patients will be advised to take a multivitamin 2 hours before or after Orlistat addition to ensure adequate nutrition.<br>|
| Active Comparator: Liraglutide + Orlistat<br> | Drug: Liraglutide + Orlistat<br>* Liraglutide will be started at 0.6 mg injected subcutaneously daily for 1 week and then increased as tolerated to 1.2 mg and then a 1.8 mg daily. Patients not tolerating a higher dose will be allowed to remain on the lower dose as long they tolerate the lower. Following titration of Liraglutide to a maximum tolerated dose, Orlistat will be started initially at a dose of 60 mg taken with evening meal. Additional doses will be added at breakfast or lunch every 1-2 weeks as tolerated. The patient will be advised to skip drug dosing if little or no fat is contained in the meal. Target dose will 60 mg three times a day.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Type 2 diabetes remission | Hemoglobin a1c will be used to assess type 2 diabetes remission. | baseline, 1 and 4 months post-randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole body insulin sensitivity | Minimal model testing will be used to assess whole body insulin sensitivity. | baseline, 1 and 4 months post-randomization | 
| GLP-1 response | A mixed meal challenge will be used to assess meal-stimulated GLP-1 response. | Baseline, 1 and 4 months post-randomization | 
| First Phase Insulin secretion | Minimal model testing will be used to assess first phase insulin secretion. | Baseline, 1 and 4 months post-randomization | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Liraglutide, Orlistat