The purpose of this study is to evaluate the effect of ISIS 449884 (ISIS-GCGRRX) on Hepatic Lipid and Glycogen Content in patients with Type 2 Diabetes being treated with Metformin.

Inclusion Criteria:

• Male or female, age 18 to 75
• BMI ≥ 25.0 kg/m2 < 36.0 kg/m2
• HbA1c ≥ 7.5% and ≤ 10.5%
• Type 2 Diabetes Mellitus and on stable dose of Metformin. Patients must have been on a stable dose of oral metformin (at least 1000 mg/day) for a minimum of 3 months prior to screening evaluation and will be required to continue their stable dose of metformin throughout the study. Patients on a stable dose of metformin plus a sulfonylurea (SU) or metformin plus a dipeptidyl peptidase-IV (DPPIV) inhibitor for a minimum of 3 months prior to Screening evaluation may be allowed
• Agree to conduct home-based (fasted) blood glucose testing as directed

Exclusion Criteria:

• Clinically significant abnormalities in medical history or physical exam
• Show evidence of uncorrected hypothyroidism or hyperthyroidism
• History of liver transplantation or renal dialysis
• History of liver disease
• History of greater than 3 episodes of severe hypoglycemia within 6 months of screening
• Treatment with any other antidiabetic drug(s) other than metformin, SU or DPPIV within 3 months of screening
• History of diabetic ketoacidosis
• Any other significant illness or condition that may interfere with the patient participating or completing the study
• Inability or unwillingness to comply with protocol or study procedures -