A Study of LY2189102 in Patients With Type 2 Diabetes

• Change from baseline to 12 weeks in fasting glucose. [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: Yes ]
• Change from baseline to 12 weeks in insulin sensitivity. [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 12 weeks in beta-cell function measured by glucose and insulin changes with the Mixed Meal Tolerance Test (MMTT). [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 12 weeks in Pharmacokinetics Cmax. [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
• Change at week 10 and week 12 in HBA1c [ Time Frame: week 10, week 12 ] [ Designated as safety issue: No ]
• Change from baseline to 12 weeks in Pharmacokinetics Area Under the Concentration Time Curve (AUC). [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 12 weeks in Pharmacokinetics measured by serum concentration. [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]

• Change from baseline to 17 week endpoint in fasting glucose. [ Time Frame: Baseline, 17 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 17 weeks endpoint in insulin sensitivity. [ Time Frame: Baseline, 17 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 17 weeks endpoint in Mixed Meal Tolerance Test (MMTT). [ Time Frame: Baseline, 17 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 20 week endpoint in PK Cmax [ Time Frame: Baseline, 20 weeks ] [ Designated as safety issue: No ]
• Change at week 10 and week 12 in HBA1c [ Time Frame: week 10, week 12 ] [ Designated as safety issue: No ]

Study to evaluate the safety, tolerability and efficacy of LY2189102 in patients with type 2 diabetes.

• Drug: LY2189102
  2 subcutaneous injections weekly for 12 weeks.
• Drug: Placebo
  2 subcutaneous injections weekly for 12 weeks.

• Experimental: 0.6mg LY2189102
  Intervention: Drug: LY2189102
• Experimental: 18mg LY2189102
  Intervention: Drug: LY2189102
• Experimental: 180mg LY2189102
  Intervention: Drug: LY2189102
• Placebo Comparator: Placebo
  0.9% Sodium Chloride
  Intervention: Drug: Placebo

Inclusion Criteria:

• Have Type 2 Diabetes and confirmed by fasting C-peptide levels greater than or equal to 0.8 ng/ml), with duration of more than 3 months.
• Body mass index between 25 and 40 kg/m2.
• Stable on diet and exercise alone, with or without metformin monotherapy (stable regimen or dose for at least 8 weeks).
• Drug-naïve or previous anti-diabetic pharmacotherapy use is allowed (for the latter, patient must have stopped taking pharmacotherapy greater than 12 weeks prior to screening and only if deemed appropriate by the investigator).
• Angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, thiazide diuretics or calcium channel blockers are permitted for the treatment of hypertension or proteinuria.
• Glycated hemoglobin level between 7% and 10%.
• Baseline High-sensitivity C-reactive protein greater than or equal to 2mg/L
• Females of childbearing potential (not surgically sterilized and between menarche and 1 year post-menopause) must test negative for pregnancy at the time of enrollment based on a pregnancy test. Furthermore, sexually active female and male participants must agree to use 2 reliable methods of birth control during the study and for 3 months following the last dose of study drug.
• Reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.

Exclusion Criteria:

• Current use of anti-diabetic pharmacotherapy (except metformin, under conditions specified in Inclusion Criteria above).
• Current treatment with anti-inflammatory drugs, including corticosteroids and non-steroidal anti-inflammatory drugs (100mg per day or less of aspirin allowed).
• Within 60 days of the initial dose of the study drug, have received treatment with a drug that has not received regulatory approval for any indication.
• Presence of autoantibodies to glutamic acid decarboxylase 65 or islet-cell autoantibody-2.
• Evidence of tuberculosis as documented by a specific assay, medical history, and chest x-ray. A specific assay, e.g., tuberculin testing, will be conducted unless it is medically inappropriate. Exceptions include patients with a history of a positive specific assay for TB who have been treated with isonicotinyl hydrazine (documented) for at least 6 months, or patients with a previous diagnosis of TB who have been appropriately treated and can provide documentation.
• Symptomatic herpes zoster within 3 months of randomization.
• Show evidence of hepatitis C and/or positive hepatitis B surface antigen.
• Show evidence of human immunodeficiency virus and/or positive test of antibodies to HIV.
• Received live or attenuated vaccine(s) within the previous 3 months prior to randomization or will receive within 3 months from the end of study.
• Screening serum creatinine greater than 2.0 mg/dL.
• Serum Asparate aminotransferase or Alanine aminotransaminase concentration greater than 2x the upper limit of normal.
• Known allergies to LY2189102 or excipients.
• Previously completed or withdrawn from this study or any other study investigating LY2189102.
• Have donated blood of greater than 500 mL within the preceding 30 days and intend to donate within 3 months from the end of study.
• Have had other recent or ongoing signs of infection (e.g. fever, current treatment with antibiotics).
• Experienced a serious bacterial infection within 6 months of randomization.
• Have a serious medical illness including but not limited to any cardiovascular, hepatic, respiratory, hematological, endocrine, or neurological disease, or any clinically significant laboratory abnormality.
• Have had lymphoma, leukemia, or any non-breast malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease.
• Have had a previous reaction to other biologics that, in the opinion of the investigator, puts patient at serious risk.