Combinatorial Therapy for Peristent Type 2 Diabetes After Gastric Banding

Type 2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01597531
• Other study ID #: ECDOI-D71
• Status: Terminated
• Phase: Phase 4
• First received: May 10, 2012
• Last updated: January 31, 2018
• Start date: June 2012
• Est. completion date: June 2014

Study information

• Verified date: January 2018
• Source: East Carolina University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Gastric Banding
• Type 2 Diabetes

Intervention

Drug:
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Brody School of Medicine at East Carolina University	Greenville	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
East Carolina University

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Type 2 diabetes remission	Hemoglobin a1c will be used to assess type 2 diabetes remission.	baseline, 1 and 4 months post-randomization
Secondary	Whole body insulin sensitivity	Minimal model testing will be used to assess whole body insulin sensitivity.	baseline, 1 and 4 months post-randomization
Secondary	GLP-1 response	A mixed meal challenge will be used to assess meal-stimulated GLP-1 response.	Baseline, 1 and 4 months post-randomization
Secondary	First Phase Insulin secretion	Minimal model testing will be used to assess first phase insulin secretion.	Baseline, 1 and 4 months post-randomization