Placebo Controlled, Dose Escalation Study in Subjects With Type 2 Diabetes Mellitus Being Treated With Sulfonylurea

Inclusion Criteria: * Type 2 diabetes mellitus of less than or equal to eight years in duration, diagnosed according to American Diabetes Association criteria * Fasting serum glucose from 150 to 270 mg/dL at screening visit * HbA1c from 7.5 to 11.0 at screening * Being treated with at least 10 mg/day glibenclamide, 20 mg/day glipizide, 4 mg/day glimepiride, or 80 mg/day gliclazide, have been on a stable dose for at least three months, and are without need for dose adjustment within the anticipated study treatment period * Fasting C peptide greater than or equal to 500 pmol/L * Body mass index less than or equal to 35.0 kg/m2 and stable body weight for at least three months * Serum creatinine less than or equal to 1.2 mg/dL for females or less than or equal to 1.5 mg/dL for males Exclusion Criteria: * Prior treatment with ISIS 113715 * Undergoing or have undergone treatment with any non marketed, therapeutic agent or device within 90 days prior to screening * Subjects who have had more than three episodes of severe hypoglycemia within six months (i.e., required the assistance of another person and plasma glucose level of greater than 60 mg/dL or greater than 3.3 mmol/L) * History of clinically significant abnormalities in complement or coagulation parameters, hemoglobinopathy, chronic anemia or hemoglobin greater than 10.5 mg/dL for females and greater than 11.5 mg/dL for males * Clinically significant complications of diabetes (e.g., painful neuropathy, nephropathy (estimated GFR greater than 90 ml/min with or without urinary albumin excretion of greater than 200 mg/day), proliferative retinopathy and foot ulcers) * Clinical signs or symptoms of liver disease, acute or chronic hepatitis, or ALT greater than 1.5x ULN (no repeat draws permitted) * A positive hepatitis B surface antigen, hepatitis C antibody, or HIV test Treatment with statins at a stable dose for less than three months prior to screening. Simvastatin dosages of up to 40 mg/day are allowed. Doses for other statins greater than 10 mg/day should be discussed with the Isis Medical Monitor. * Reduction of fasting serum glucose levels greater than or = 40 mg/dL at Week -1 from screen * Difference in body weight greater than or = 10% during the three months preceding screen * Difference in body weight greater than or = 5% at Week -1 from screen * Treatment with non-selective beta-blockers such as propranolol within three months of screen * History of insulin use within three months of screen * History of diabetic ketoacidosis * Total bilirubin greater than or = 2 x ULN