Effect of Gastric Bypass on the Absorption of Metformin (ABSORB-Met)

Background: Gastric bypass is the most commonly performed type of bariatric (obesity) surgery, has dramatically increased in popularity and is now considered to be preferred treatments in severely obese patients that fail non-surgical therapy - particularly in patients with type 2 diabetes. Drug malabsorption is a potential concern post-gastric bypass because intestinal length is reduced.

Purpose: The purpose of this controlled, pharmacokinetic study is to determine whether the absorption of a single dose of metformin, the first line drug treatment in patients with type 2 diabetes, is significantly reduced after gastric bypass.

Methods: A single dose of standard release metformin 1000 mg will be administered to patients who have undergone gastric bypass and to patients who have not received surgery but are on the wait list (wait-listed controls). Blood sampling and urine sampling will occur in standardized fashion over the ensuing 24 hours to measure and compare the absorption of metformin between study arms. 34 patients total will be recruited.

Significance: Following completion of this study, we will better understand how gastric bypass affects metformin absorption. Ultimately, this information will help to ensure that this patient population is receiving optimal doses of this important drug treatment.

Study Overview

• Status: Completed
• Conditions: Obesity; Gastric Bypass

• Study Type: Observational
• Enrollment (Anticipated): 34

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G2B7
      • University of Alberta Hospital Clinical Investigation Unity

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Post gastric bypass and obese controls

1. Male and Female
2. 18 - 60 years old
3. ≥ 3 months post-RYGB surgery or wait listed for bariatric surgery
4. Able to provide written informed consent.

Description

Inclusion Criteria:

Patients living within and around Edmonton that have been referred to the Alberta Health Services Weight Wise Program

Exclusion Criteria:

1. Undergone or undergoing revision of a previous bariatric procedure
2. Any major post-operative gastrointestinal complications, such as an anastomotic leak, outlet obstruction or persistent vomiting
3. Currently on metformin therapy

4. Any contraindications to metformin therapy such as:

   1. allergy to the drug
   2. chronic metabolic acidosis
   3. history of lactic acidosis
   4. liver failure or baseline liver enzymes higher than 3-fold above the upper limit of normal
   5. congestive heart failure
   6. renal failure (glomerular filtration rate < 60 ml/min)
   7. alcoholism
   8. acute illness
   9. fatty liver disease
5. Pregnant or nursing
6. Not taking furosemide or nifedipine (both drugs may increase metformin absorption by 15-20%)the day of visit 2.
7. Any other medical, social or geographic condition, which, in the opinion of the investigator would not allow safe completion of the study protocol

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Post Gastric Bypass
Obese Controls; age, BMI, gender matched

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area-under-the-curve of metformin absorption (0-infinity)	cross-sectional

Secondary Outcome Measures

Outcome Measure	Time Frame
AUC (0-24h)	cross-sectional
tmax	cross-sectional
cmax	cross-sectional
AUC glucose (0-8h)	cross-sectional
bioavailability of metformin (urine metformin concentration from 0-infinity)	cross-sectional

Collaborators and Investigators

• Sponsor: University of Alberta
• Investigators: Principal Investigator: Raj Padwal, MD, University of Alberta

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: November 12, 2009
• First Submitted That Met QC Criteria: November 12, 2009
• First Posted (Estimate): November 13, 2009

Study Record Updates

• Last Update Posted (Estimate): March 3, 2011
• Last Update Submitted That Met QC Criteria: March 2, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: obesity; pharmacokinetics; metformin; gastric bypass; absorption
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: RES0002122