• To compare the effect on glucose control of exenatide LAR administered weekly by subcutaneous (SC) injection to that achieved by exenatide administered SC twice a day (BID) [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
• To examine the safety and tolerability of exenatide LAR administered SC weekly [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
• To examine glucose control during the transition from treatment with exenatide administered SC BID to exenatide LAR administered SC weekly [ Time Frame: transition period ] [ Designated as safety issue: No ]

• To compare the effect on glucose control of exenatide LAR administered weekly by subcutaneous (SC) injection to that achieved by exenatide administered SC twice a day (BID)
• To examine the safety and tolerability of exenatide LAR administered SC weekly
• To examine glucose control during the transition from treatment with exenatide administered SC BID to exenatide LAR administered SC weekly

• To examine the effects of exenatide LAR administered SC weekly on pharmacokinetics and various pharmacodynamic parameters [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
• To examine the incidence and rate of hypoglycemic events associated with the proactive approach to sulphonylurea management [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
• To examine the long-term safety and tolerability and effect on glucose control of exenatide LAR administered SC weekly [ Time Frame: open ended ] [ Designated as safety issue: No ]

• To examine the effects of exenatide LAR administered SC weekly on pharmacokinetics and various pharmacodynamic parameters
• To examine the incidence and rate of hypoglycemic events associated with the proactive approach to sulphonylurea management
• To examine the long-term safety and tolerability and effect on glucose control of exenatide LAR administered SC weekly

The purpose of this study is to examine the effects of exenatide long-acting release (LAR) on glucose control and safety in subjects with type 2 diabetes mellitus managed with diet modification and exercise and/or oral antidiabetic medications.

• Drug: exenatide, long acting release
• Drug: exenatide

Inclusion Criteria:

• Has type 2 diabetes mellitus treated with diet modification and exercise alone or in combination with a stable regimen of a combination of metformin, sulphonylureas, and thiazolidinediones for a minimum of 2 months at screening.
• Hemoglobin A1c (HbA1c) of 7.1% to 11.0%, inclusive, at screening.
• Body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive, at screening.

Exclusion Criteria:

• Has been previously exposed to exenatide (Byetta®), exenatide LAR, or any glucagon-like peptide-1 (GLP-1) analog.
• Received any investigational drug or has participated in any type of clinical trial within 30 days prior to screening.

• Has been treated, is currently treated, or is expected to require or undergo treatment with any of the following excluded medications:

  • Alpha glucosidase inhibitor or meglitinide within 30 days of screening;
  • Insulin within 2 weeks prior to screening or insulin for longer than 1 week within 3 months of screening;
  • Regular use (> 14 days) of drugs that directly affect gastrointestinal motility;
  • Regular use (> 14 days) of systemic corticosteroids by oral, intravenous, or intramuscular route; or potent, inhaled, or intrapulmonary steroids known to have a high rate of systemic absorption;
  • Regular use (> 14 days) of medications with addictive potential such as opiates and opioids;
  • Prescription or over-the-counter weight loss medications within 6 months of screening.