A Study in Patients With Type 2 Diabetes

A 12-Week, Phase 2, Randomized, Double-Blind, Active-Controlled Study of LY2608204 Given as Monotherapy or in Combination With Metformin in Patients With Type 2 Diabetes Mellitus

The study is designed to see if once daily oral dosing of LY2608204 will help control diabetes as measured by the glycosylated fraction of hemoglobin A (HbA1c) level. It will also help to determine the safety of the medication and the most useful doses of the medication.

Inclusion Criteria:

• Clinical diagnosis of type 2 diabetes mellitus prior to entering the trial

• May be treated with:

  1. Diet and exercise alone or
  2. Diet and exercise in combination with a stable dose of metformin for at least 3 months before Screening or
  3. Diet and exercise in combination with a stable dose of sulfonylurea or meglitinide (repaglinide, nateglinide) for at least 3 months before Screening or
  4. Diet and exercise in combination with stable doses of metformin and sulfonylurea or metformin and meglitinides for at least 3 months before Screening and have had diabetes for at least 6 years

• Must have an Hemoglobin A1c value between 7% and 10%

• Must have a body mass index (BMI) between 20 and 40 kg/m2

• Must have stable weight during the 3 months prior to Screening (weight change not to exceed 5 kg (11 lb))

• If female, you must not be able to get pregnant

• Must be well motivated, capable, and willing to complete study required glucose monitoring and instruction

Exclusion Criteria:

• Use of insulin or any antidiabetic agent other than metformin or sulfonylurea or meglitinide during the 3 months prior to Screening
• Have a gastrointestinal disease that significantly impacts gastric emptying or motility or have undergone gastric bypass or gastric banding surgery
• Have had more than one episode of severe hypoglycemia within 6 months prior to entry into the study, or are currently diagnosed as having hypoglycemia unawareness or have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months
• Are currently taking or have taken within the last 2 months, prescription or over-the counter medications which affect body weight
• Have cardiac disease with functional status that is New York Heart Association [NYHA] 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, 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 a QTcB (Bazett's-corrected QT interval) interval greater than 450 msec for men or greater than 470 for women at Screening or any personal history of ventricular tachycardia or unexplained syncope
• Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or significantly elevated liver blood tests
• Are currently receiving renal dialysis, have a serum creatinine greater than 2.0 mg/dL (177 μmol/L) or a calculated creatinine clearance of less than 60 ml/min or in patients being treated with metformin, have other known contradictions to metformin use including, but not limited to, a serum creatinine above (or creatinine clearance below) what is approved in the metformin product label
• Have fasting state hypertriglyceridemia (defined as greater than 5.65 mmol/L, 500 mg/dl) at Screening. If taking lipid-lowering agents, doses of these medications must be stable for 30 days prior to randomization.
• Are receiving chronic (for more than 2 weeks) systemic glucocorticoid therapy (excluding topical or inhaled preparations) or have received such therapy within 4 weeks immediately prior to Randomization
• 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
• Have a history of seizure disorder
• Are currently using or intend to use inhibitors of Cytochrome P450 family 3A (CYP3A4)
• Currently taking a medication that is a sensitive substrate of the CYP3A4 pathway with a narrow therapeutic index