A 12-week Study To Evaluate PF-06291874 Once a Day in Adults With T2DM Inadequately Controlled On Metformin

This will be a randomized, double blind, stratified, placebo controlled, parallel group
study conducted in T2DM subjects receiving background metformin therapy. Subjects will
complete screening procedures to determine eligibility, followed by an 8 week metformin
stabilization period prior to randomization. In addition, subjects taking other OADs, in
combination with metformin, will undergo a washout during this period, in which non
metformin OAD medications will be temporarily discontinued for the duration of the trial.
Following confirmation of study eligibility criteria at randomization, subjects will be
stratified into 2 groups based on the use of concomitant statin therapy. Each stratum will
be randomized across treatment groups, such that the number of subjects taking concomitant
statin therapy and those not taking statin therapy will be approximately balanced across
treatment groups.

Inclusion Criteria:

1. Males or non-childbearing potential females between the ages of 18 (or the minimum
country specific age of consent if >18) and 70 years, inclusive, at the screening
visit (V1) with the diagnosis of T2DM;Female subjects who are not of childbearing
potential

2. Subjects who have been on a stable dose of metformin either alone or in combination
with one additional acceptable OAD

3. HbA1c at the Screen Visit (V1), as assessed by study specific central laboratory, is
7-11% if on metformin monotherapy; is 6.5-9.5% if on dual combination therapy
(metformin plus 1)

Exclusion Criteria:

1. Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes;

2. Fasting plasma glucose levels >270 mg/dL (15.0 mmol/L) at the screening and run in
visit, (as assessed by study specific central laboratory) confirmed by a single
repeat, if deemed necessary

3. History of myocardial infarction, unstable angina, arterial revascularization,
stroke, New York Heart Association Functional Class III IV heart failure, or
transient ischemic attack within 6 months of screening;

4. Any medical condition possibly affecting study drug absorption (eg, gastrectomy or
any area of intestinal resection, active inflammatory bowel disease or pancreatic
insufficiency

5. Subjects with a creatinine clearance <60 mL/min as determined by the Cockcroft Gault
equation (listed below) using serum creatinine measured at screening, confirmed via a
single repeat, if deemed necessary

6. Subject with a positive result for hepatitis B surface antigen (HBsAg), hepatitis B
core antibodies (HBc Ab) or hepatitis C virus (HCV) antibodies

7. Screening seated systolic blood pressure >160 mm Hg and/or diastolic blood pressure
>105 mm Hg after at least a 5 minute rest. Blood pressure determined as the mean of
triplicate measurements collected with approximately 2 minutes of rest between
measurements

8. Screening supine 12 lead ECG demonstrating a corrected QT (QTc) >470 msec; or a QRS
interval >120 msec. If QTc exceeds 470 msec or QRS exceeds 120 msec, the ECG may be
repeated 2 more times with an interval of 2-4 minutes between each measurement and
the mean of the 3 values used to determine the subject's eligibility

9. Subjects with an arm circumference >52 cm measured at the midpoint of the length of
the upper arm;

10. History (within the last 6 months) of regular alcohol consumption exceeding 14 drinks
per week for men and 7 drinks a week for women. (1 drink = 5 ounces of wine (150 mL)
or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor);

11. Treatment with thiazolidinediones (TZDs), or subcutaneously administered anti
diabetic agents (eg, insulin, exenatide, liraglutide, pramlintide) within 6 weeks
prior to V1;

12. Subjects with a known hypersensitivity or intolerance to a glucagon receptor
antagonist, or known prior participation in a trial involving PF 06291874;