• To evaluate the safety and tolerability of ISIS 113715
  
• To evaluate the pharmacokinetic profile of ISIS 113715
  
• To evaluate the pharmacologic activity of ISIS 113715
  

Inclusion Criteria:

• Type 2 Diabetes Mellitus of less than 5 years in duration
• Have never received hypoglycemic therapy
• Aged 18 to 65 years
• Fasting blood glucose between 130 and 220 mg/dL (7.2 to 12.2 mmol/L) for Cohorts A-D and between 140 and 220 mg/dL (7.8 to 12.2 mmol/L) for Cohort E
• HbA1c between 6.8 and 10.0% for Cohorts A-D and between 7.5 and 11.0% for Cohort E
• Body Mass index > 25 and < 35 kg m -2

Exclusion Criteria:

• Medication that may affect glucose homeostasis (e.g. systemic glucocorticoid) within one month of screening
• Clinically significant abnormalities in medical history or physical exam
• Clinically significant abnormalities on laboratory examination
• History of HIV infection
• Active infection requiring antiviral or antimicrobial therapy
• Malignancy (with the exception of basal or squamous cell carcinoma of the skin if adequately treated and no recurrence for > one year at the time of screening)
• Any other concurrent condition which, in the opinion of the Investigator, would preclude participation in or interfere with compliance
• Alcohol or drug abuse
• Undergoing or have undergone treatment with another investigational drug, biologic agent or device within 90 days of screening
• Abnormal serum creatinine concentration defined as > 1.5 mg/dL (132.6 micro mol/L) for males and > 1.2 mg/dL (106 micro mol/L) for females
• Medications that may affect coagulation (heparin, warfarin, etc.) with the exception of acetylsalicylic acid or non-steroidal anti-inflammatory agents.
• Allergy to sulfur-containing medications