A Phase 1 Study to Evaluate the Effect of GSK256073, an HM74A Receptor Agonist, on Glucose and NEFA Levels in Type 2 Diabetics

This is a multi-center study that will enroll approximately 36 subjects. The study consists
of three periods of two days of dosing each. The study will evaluate 5 potential dose
regimens. Each subject will receive a randomized sequence of treatments over three periods,
with placebo treatment in one period and two different active dose regimens in the other two
periods. There will be 5 to 12 days of outpatient washout between treatment periods.
Subjects will continue their current treatment on metformin throughout the study. Subjects
will monitor blood glucose levels daily via glucometer during oupatient washout periods. A
follow-up visit will occur between 5 and 10 days after the last period of the study.

Inclusion Criteria:

- Subjects with documented (not less than 6 months prior to screening) type 2 diabetes
mellitus diagnosis with:

- HbA1c levels greater than 6.5 percent and less than or equal to 9.5 percent at
screening,

- On monotherapy with metformin at the time of screening, and at a todal daily dose
greater than or equal to 1000 mg at the time of dosing,

- Fasting plasma glucose level less than 270 mg/dl at screening

- Male or female between 20 and 70 years of age inclusive, at the time of signing the
informed consent

- Waist circumference above 102cm (40 inches) for men, and 88cm (35 inches) for women

- Fasting triglycerides between 150 mg/dl and 500 mg/dl, inclusive

- BMI within the range of 22-37 kg/meter squared, inclusive

Exclusion Criteria:

A subject will not eligible for inclusion in this study if any of the following criteria
apply:

- Requiring insulin therapy or use of combination oral antidiabetic medications or use
of monotherapy other than metformin within the 3 months prior to screening

- Past or present disease (other than type 2 diabetes mellitus) that in the opinion of
the Investigator may affect the outcome of this study. These diseases include the
following but are not limited to, cardiovascular disease, malignancy, hepatic
disease, renal disease, hematological disease, neurological disease, gastrointestinal
disease and endocrine disease

- A positive pre-study Hepatitis B surface antigen, or positive Hepatitis C or HIV
antibody result within 3 months of screening

- Renal impairment as defined by a calculated GFR less than 60 ml/min

- Any concurrent serious illness (e.g., severe COPD, history of malignancy other than
skin cancer within 5 years of initial diagnosis or with evidence of recurrence) that
may interfere with a subject completing the study

- Clinical laboratory values as defined per protocol

- ECG parameters as defined per protocol

- History of gout and/or hyperuricemia/uric acid kidney stone or treated with drugs for
hyperuricemia: allopurinol and/or probenecid

- Current or chronic history of liver disease, or known hepatic or biliary
abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)

- Use of the following blood pressure medications or other medications renally excreted
via OAT is prohibited: Enalapril (at any dose), Losartan (at any dose), Captopril (at
any dose)

- Pregnant females as determined by positive serum hCG test at screening or positive
urine hCG test prior to dosing

- Lactating females