Combinatorial Therapy for Peristent Type 2 Diabetes After Gastric Banding

NCT ID: NCT01597531

Last Updated: 2018-02-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2014-06-30

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.

Conditions

Type 2 Diabetes; Gastric Banding

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Liraglutide only

Group Type: ACTIVE_COMPARATOR

Liraglutide

Intervention Type: DRUG

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.

Orlistat only

Group Type: ACTIVE_COMPARATOR

Orlistat

Intervention Type: DRUG

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.

Liraglutide + Orlistat

Group Type: ACTIVE_COMPARATOR

Liraglutide + Orlistat

Intervention Type: DRUG

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.

Interventions

Liraglutide

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.

Intervention Type: DRUG

Orlistat

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.

Intervention Type: DRUG

Liraglutide + Orlistat

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

East Carolina University

OTHER

Sponsor Role: lead

Responsible Party

Moahad S Dar

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Brody School of Medicine at East Carolina University

Greenville, North Carolina, United States

Countries

United States

References

Buchwald H, Estok R, Fahrbach K, Banel D, Jensen MD, Pories WJ, Bantle JP, Sledge I. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009 Mar;122(3):248-256.e5. doi: 10.1016/j.amjmed.2008.09.041.

Reference Type: BACKGROUND

PMID: 19272486 (View on PubMed)

Other Identifiers

ECDOI-D71

Identifier Type: -

Identifier Source: org_study_id