This is a phase 2a, multicenter, randomized, double-blind, placebo-controlled, parallel group, fixed dose study. AMG 151 will be evaluated in subjects with type 2 diabetes treated with metformin for at least 3 months prior to randomization.

Inclusion Criteria:

• Age 18 to 75 years, inclusive
• Diagnosis of type 2 diabetes mellitus
• HbA1c levels 7.5% to 11.0%, inclusive, at screening
• Fasting C-peptide levels ≥ 0.2 nmol/L at screening
• BMI ≥ 25 to < 45 kg/m2 at screening
• Treated with metformin monotherapy for at least 3 months prior to randomization; the metformin dose must be ≥ 850 mg daily for at least 2 months immediately prior to randomization
• If a subject is being treated for hyperlipidemia or hypertension they should be on stable medication for 30 days before randomization
• Subject has provided informed consent.

Exclusion Criteria:

• History of type 1 diabetes
• History of significant weight gain or loss (> 10%) during the 4 weeks before randomization
• Use of any weight loss medication (over the counter or prescription) within 60 days of randomization
• Use of any oral or injectable anti-hyperglycemic medication (other than metformin) within 3 months prior to randomization
• Use of chronic and/or continuous insulin administration for > 15 days in an outpatient setting to achieve and maintain glycemic control prior to randomization
• Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months
• Have had more than 1 episode of severe hypoglycemia within 6 months prior to entry into the study, or currently diagnosed as having hypoglycemia unawareness
• Evidence of active infections that can interfere with the study
• Presence of clinically significant organ system disease that is not stabilized or may interfere with the study
• Currently receiving immunosuppressive therapy
• History of positive HIV, chronic hepatitis B or C, or cirrhosis
• Have symptomatic congestive heart failure or a history of myocardial infarction, unstable angina, or decompensated congestive heart failure or stroke in the past 6 months prior to screening.
• History of gastric surgery, vagotomy, bowel resection or any surgical procedure that might interfere with gastrointestinal motility, pH or absorption
• Any finding on the screening ECG that in the opinion of the investigator requires further cardiovascular evaluation
• Poorly controlled hypertension defined as diastolic pressure > 100 mm Hg or systolic pressure > 160 mm Hg (assessed on two separate occasions during the screening period)
• Malignancy (other than resected cutaneous basal or cutaneous squamous cell carcinoma, or treated in situ cervical cancer considered cured) within 5 years of screening visit (if a malignancy occurred > 5 years ago, subject is eligible with documentation of disease-free state since treatment)
• Use of known inhibitors or inducers of CYP3A4 are not permitted 30 days prior to randomization