A Study of GSK256073 in Subjects With Type 2 Diabetes Mellitus Who Are Being Treated With Metformin

The study will be conducted at centers in Europe and the United States. The study is being
conducted in two parts. Part A (n = 90 subjects) will provide a preliminary evaluation of 12
weeks of treatment. Initiation of part B (n = 210 additional subjects) will be dependent on
the results observed in part A. The emerging data from part A will be used to guide selection
of the doses in Part B. Up to 8 dose levels of GSK256073 may be included in part B. The
emerging exposure response relationships from the part A interim analysis will be used to
guide dose selection.

Each subject enrolled in the study will undergo screening procedures, a 2 week placebo run-in
period, baseline assessments, randomization, a twelve week treatment period, and a 2 week
follow-up period. Following completion of the baseline visit and randomization into the
study, subjects will return to the clinic for safety and efficacy assessments at Weeks 3, 6,
9, and 12. A subject's total participation in the study will last up to approximately 20
weeks. Subjects will continue their current prescribed regimen of metformin (glucophage)
monotherapy and will monitor fasting blood glucose levels daily using a glucometer.

Inclusion Criteria:

- A diagnosis of T2DM as determined by a responsible physician based on a medical
evaluation including medical history, physical examination, and laboratory tests, with
onset at least 6 months prior to Screening. Subjects may be entered if they have
stable hypertension or dyslipidemia on therapy. Subjects with other conditions except
as noted in the Exclusion criteria may be included only if the investigator and GSK
medical monitor agree that the condition is unlikely to introduce additional risk
factors and will not interfere with study procedures

- HbA1c levels greater than or equal to 7.0 % and less than or equal to 9.5% at
Screening

- On monotherapy with metformin at the time of screening, and at a maximum tolerated
dose greater than or equal to 1000 mg for at least 2 months prior to dosing.

- Fasting plasma glucose level less than 13.3 mmol/L (240 mg/dL) at Screening

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

- Fasting Triglycerides lower than 4.52 mmol/L (400 mg/dL)

- A female subject is able to participate is she if of non-child bearing potential

- Male subjects must agree to use one of the contraception methods listed in the
protocol. This criterion must be followed from the time of the first dose of study
medication until 3 days after last dose of the study medication

- Overweight with BMI greater than or equal to 25 kg/m2 for non-Asian Indians and
greater than or equal to 24 kg/m2 for Asian-Indian, and less than 40 kg/m2

- The subject is capable of giving written informed consent, which includes compliance
with the requirements and restrictions listed in the consent form

- Subjects in France will be eligible only if they are affiliated to or a beneficiary of
a social security category

- Subjects in other countries must meet all local and/or country-specific requirements
for registration and reimbursement, as applicable

Exclusion Criteria:

- 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

- A positive pre-study Hepatitis B surface antigen, or positive Hepatitis C 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

- Laboratory values as defined per protocol

- ECG criteria as defined per protocol

- Systolic blood pressure greater than 160 mmHg, or diastolic blood pressure greater
than 100 mmHg at Screening

- History of uric acid kidney stone, and being treated with drugs for hyperuricemia
including Allopurinol or Probenecid

- History of peptic ulcer disease (PUD) and/or other gastrointestinal bleeding within
the 12 months prior to screening

- Use of certain blood pressure medications or certain other medications that are
renally excreted as defined per protocol

- History of myopathy or CPK value greater than 3 times upper limit of normal at
screening

- The subject has participated in a clinical trial and has received an investigational
product within 30 days or 5 half-lives or twice the biological effect (whichever is
longer)

- Exposure to more than four new chemical entities within 12 months prior to the first
dosing day

- Any change in diet, exercise habits or smoking status within six weeks prior to
screening. Any subject that cannot refrain from smoking while in the unit must be
excluded

- History of sensitivity to any of the study medications, including sitagliptin or
metformin, or components thereof or a history of drug or other allergy that, in the
opinion of the investigator or GSK Medical Monitor, contraindicates their
participation

- The subject has a positive pre-study drug screen

- History of regular alcohol consumption within 6 months of the study as defined per
protocol

- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period

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

- Lactating females

- Subjects who are unwilling or unable to follow the procedures outlined in the protocol

- Subject is mentally or legally incapacitated