Safety and Efficacy Study of Metaglidasen in Type 2 Diabetes in Patients Suboptimally Controlled on Insulin

Inclusion Criteria

• •Type 2 diabetes (as described by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus24) treated with insulin alone (a stable dose of long and/or intermediate-acting insulin or pre-mixed insulin e.g., "70/30") ≥ 30 units/day for at least 3 months, but poorly controlled on their existing therapy
• •Or, patients treated with insulin (as above) in combination with non-TZD hypoglycemic agents (e.g., a sulfonylurea, metformin, acrabose, or Byetta for at least 3 months, but poorly controlled on their existing therapy
• •Or, patients treated with fixed doses of short-acting insulin in combination with intermediate-acting insulin for at least 3 months, but poorly controlled on their existing therapy
• •Patients in last 2 categories must be willing to discontinue the use of OHA and/or short-acting insulin (or change to pre-mixed insulin) for at least 26 weeks.
• •Male or female, 18-75 years of age
• •Provide informed consent and agree to comply with study requirements
• •Current monotherapy insulin dose regimen ≥ 30 units/day (stable for 8-week Run-in/stabilization Period); or patients who need insulin dose adjustment must have a stabilized dose ≥ 30 units/day. Patients must not have taken TZDs within 5 months of screening
• •All female patients must be surgically sterile, post-menopausal (at least 40 years of age with no history of menses for at least 2 years) or agree to use adequate contraception(s) that must include a barrier method (other methods may include oral contraceptives, double barrier methods, intra-uterine devices, or abstinence). Depo contraceptives are excluded
• •Female patients must not be pregnant or lactating
• •BMI 26-44 kg/m2
• •Hemoglobin A1c must be ≥7.5%, ≤11.5% at both Screening and Visit 4
• •Patients must have a FPG ≤ 220 mg/dl
• •Patients must have liver function tests ≤ 2X the upper limits of normal for AST, ALT, and bilirubin, and ≤ 2.5X the upper limits of normal for ALP and GGT
• •Patients must have serum creatinine ≤ 1.8 mg/dl for males and ≤ 1.5 mg/dl for females and BUN ≤ 40 mg/dl
• •Fecal occult blood test must be negative
• •All other clinical laboratory parameters must be within normal limits or considered not clinically significant for participation in this study, including: hematology, coagulation, other serum chemistry, and other urinalysis parameters
• •TSH must be ≤ 3x ULN and patient clinically euthyroid in opinion of investigator. If TSH is \> ULN but ≤ 3x ULN, and patient is clinically euthyroid, FT4 should be drawn and must be WNL
• •Electrocardiogram (ECG) must be normal, or considered not clinically significant, for participation in this study
• •Patients must have a blood pressure ≤ 160/90 mm/hg including hypertensive patients controlled with medication