Effect of Metformin on Gut Peptides , Bile Acids and Lipid Profiles in Type 2 Diabetics

type two diabetics

Inclusion Criteria:

1. T2DM men and women between 18 -70 years of age on stable dose of metformin
2. Subjects taking stable regimens of aspirin, ACE inhibitors, beta-blockers, calcium channel blockers, thyroid replacement hormone, and HMG-CoA reductase inhibitors (statins) will be allowed if their dose regimen(s) remain constant throughout the study period
3. HBA1C >6.5% <8.5%
4. BMI from 22.5 up to 37.5 kg/m2, inclusive
5. AST, ALT, alkaline phosphatase and bilirubin less than or equal to 3xULN
6. Has a normal ECG as determined by unit physician.
7. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

1. medically unable or unwilling to discontinue current metformin therapy for as required by the protocol and remain off medication until the completion of Visit 3
2. past or present disease (other than T2DM) as judged by the Investigator, which may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, neurological disease and endocrine disease.
3. subject is currently on bile acid sequestrant therapy.
4. Gastrointestinal surgery or disease that would compromise the use of the EnteroTest
5. fasting triglycerides >450mg/dL (>5.1 mmol/L)
6. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
7. A positive pre-study drug/alcohol screen.

8. History of regular alcohol consumption within 6 months of the study defined as:

   -An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.

9. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
10. Pregnant females as determined by positive (serum or urine) hCG test at screening or prior to dosing.
11. Lactating females.
12. Unwillingness or inability to follow the procedures outlined in the protocol.

12.Subject is mentally or legally incapacitated or unable to provide informed consent