The purpose of this study is to help answer the following research question(s):

• To test if taking LY2599506 for 12 weeks controls blood sugar better than taking glyburide for 12 weeks.
• To evaluate the safety of LY2599506 in subjects with diabetes.
• To determine if LY2599506 has the ability to control blood sugar in subjects with diabetes.
• To determine how much LY2599506 should be given to subjects.
• To determine if LY2599506 has an effect on a subject's weight.

The study design consists of 4 study periods: a screening period, a 4-week dose adjustment period, an 8 week treatment period, and a 4-week follow up period.

• Drug: LY2599506
  Administered orally, twice daily prior to morning and evening meals for 12 weeks
  Other Name: Glucokinase Activator 1
• Drug: Glyburide
  Administered orally, twice daily prior to morning and evening meals for 12 weeks
• Drug: Placebo
  Administered orally, twice daily prior to morning and evening meals for 12 weeks

• LY2599506: Experimental
  Combinations of 50 or 100 mg capsules of LY2599506 or matching placebo capsules (each dose contains at least one capsule of active drug). LY2599506 will be administered in escalating doses from 100 mg/day up to 800 mg/day
  Interventions:

  • Drug: LY2599506
  • Drug: Placebo
• Glyburide: Active Comparator
  Combinations of 2.5 mg capsules of Glyburide or matching placebo capsules (each dose contains at least one capsule of active drug). Glyburide will be administered in escalating doses from 5 mg/day up to 20 mg/day
  Interventions:

  • Drug: Glyburide
  • Drug: Placebo

Inclusion Criteria:

• Have type 2 diabetes mellitus prior to entering the trial
• Are currently being treated with diet and exercise therapy consistent with the local standards of medical care
• Treated with: Diet and exercise alone or Diet and exercise in combination with a stable dose of metformin for at least 3 months prior to entering the trial or Diet and exercise in combination with a stable dose of sulfonylurea for at least 3 months prior to entering the trial or Diet and exercise in combination with stable doses of metformin and sulfonylurea for at least 3 months prior to entering the trial and have had diabetes for at least 6 years.
• Have an HbA1c value between 7% and 10%
• Are women not of child-bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Male patients will be advised to use a reliable method of birth control during the study and until 3 months after the last dose of study medication if their partner is of child-bearing potential.

Exclusion Criteria:

• Use of insulin or any antidiabetic agent other than metformin or sulfonylurea during the 3 months prior to entering the trial.
• Have a gastrointestinal disease that significantly impacts gastric emptying or motility (for example, severe gastroparesis or pyloric stenosis), in the opinion of the Investigator, or have undergone gastric bypass or gastric banding surgery.
• Have had more than 1 episode of severe hypoglycemia within 6 months prior to entry into the study, or are currently diagnosed as having hypoglycemia unawareness
• Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months.
• Have cardiac autonomic neuropathy (for example, resting tachycardia or orthostatic hypotension), based on clinical signs, symptoms, or appropriate diagnostic testing.
• Have cardiac disease with functional status that is New York Hearth Association Class II, III, or IV or a history of myocardial infarction, unstable angina, or decompensated congestive heart failure in the past 6 months.
• Have poorly controlled hypertension (that is, mean systolic blood pressure >160 mm/Hg or mean diastolic blood pressure >100 mm/Hg) history of malignant hypertension, evidence of renal artery stenosis and/or evidence of labile blood pressure including symptomatic postural hypotension. Doses of antihypertensive medications must be stable for 30 days before randomization.
• Have fed or fasting state hypertriglyceridemia (defined as >6.8 mmol/L, 600 mg/dl) at screening. If taking lipid-lowering agents, doses of these medications must be stable for 30 days prior to randomization.
• Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or repeated alanine transaminase (ALT) levels >2.5 times the upper limit of the reference range at screening.
• Have evidence of a significant active, uncontrolled endocrine or autoimmune abnormality, as judged by the Investigator at screening.
• Have an active or untreated malignancy or have been in remission from a clinically significant malignancy (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years.