The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-04991532 following multiple (14 days) escalating oral doses in patient wtih type 2 diabetes.

Safety/Tolerability, PK, and PD

Inclusion Criteria:

• Patients with type 2 diabetes mellitus who are taking metformin only. Treatment should be stable, where this is defined as no change in the treatment, including dose, over the past 2 months. Subjects treated with a sulfonylurea (SU) or a dipeptidyl peptidase-4 inhibitor (DPP-4i) in combination with metformin may be eligible if washed off the SU or DPP-4i to metformin only for a minimum of 4 weeks before dosing. Subjects being switched over from an SU and metformin or a DPP-4i and metformin to metformin only will still need to meet the fasting glucose requirements on Day -2 as defined in the protocol.
• Body Mass Index (BMI) of 18.5 to 45.0 kg/m2; and a total body weight >50 kg (110 lbs).
• Fasting C-peptide >0.8 ng/mL.
• HbA1c >/=7% and >/=10%. If the patient requires to be washed off an SU or DPP-4i, the HbA1c limits will be >/=6.5% and </=9%.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease. Subjects who have chronic conditions other than T2DM (for example, hypercholesterolemia or hypertension) but are controlled by either diet or stable (for the last 2 months) doses of medications may be included as well.
• Evidence or history of diabetic complications with significant end-organ damage.
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• History of stroke, transient ischemic attack, or myocardial infarction within the past 6 months.
• History of coronary artery bypass graft or stent implantation.
• Clinically significant peripheral vascular disease.
• Any history or clinical evidence of congestive heart failure, NYHA Classes II-IV.
• Current history of angina/unstable angina.
• ECG findings suggestive of asymptomatic myocardial ischemia or QTc >470 msec at screening.
• One or more self-reported episodes of hypoglycemia within the last 3 months, or two or more self-reported episodes of hypoglycemia within the last 6 months.
• Screening or Day -2 fasting (>/=8 hours) glucose, </=90 or >/=270 mg/dL, confirmed by a single repeat if deemed necessary.
• A positive urine drug screen.
• Use of tobacco or nicotine-containing products in excess of the equivalent of 10 cigarettes per day.
• History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening.
• Certain concomitant medications are excluded, as defined in the protocol.
• Screening supine blood pressure >/=160 mm Hg (systolic) or >/=100 mm Hg (diastolic).
• Certain laboratory values (for example, triglyceride and liver function test results).
• Pregnant or nursing females; females of childbearing potential.