Efficacy and Safety Study of Alogliptin and Insulin in the Treatment of Type 2 Diabetes.

Inclusion Criteria

• Diagnosis of type 2 diabetes mellitus and currently treated with insulin alone (with or without metformin), and is inadequately controlled. Metformin dose must be stable for at least 8 weeks prior to Randomization.
• No treatment with antidiabetic agents other than insulin and metformin within the 8 weeks prior to Randomization.
• Body mass index greater than or equal to 23 kg/m2 and less than or equal to 45 kg/m2
• Fasting C-peptide concentration greater than or equal to 0.8 ng per mL. (If this screening criterion is not met, the subject still qualifies if C-peptide greater than or equal to 1.5 ng per mL after a challenge test).
• Glycosylated hemoglobin concentration greater than or equal to 8.0% at Screening.
• Using a stable dose of insulin of at least 15 units but not more than 100 units per day for at least 8 weeks prior to Randomization. A dose of insulin that varies by up to 15% of the mean will be considered as stable.
• If regular use of other, non-excluded medications, must be on a stable dose for at least the 4 weeks prior to Screening. However, as needed use of prescription or over-the-counter medications is allowed at the discretion of the investigator.
• Systolic blood pressure less than or equal to180 mm Hg and diastolic pressure less than or equal to 110 mm Hg
• Hemoglobin greater than or equal to 12 g per dL for males and greater than or equal to10 g per dL for females.
• Alanine aminotransferase less than or equal to 3 times the upper limit of normal.
• Serum creatinine less than or equal to 2.0 mg per dL.
• Thyroid-stimulating hormone level less than or equal to the upper limit of the normal range and the subject is clinically euthyroid.
• Neither pregnant (confirmed by laboratory testing in females of childbearing potential) nor lactating.
• Female subjects of childbearing potential must be practicing adequate contraception. Adequate contraception must be practiced for the duration of participation in the study.
• Able and willing to monitor own blood glucose concentrations with a home glucose monitor
• No major illness or debility that in the investigator's opinion prohibits the individual from completing the study
• Able and willing to provide written informed consent

Exclusion Criteria

• Urine albumin to creatinine ratio of greater than 1000 μg per mg at Screening. If elevated, the subject may be rescreened within 1 week.
• History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 5 years prior to Screening. (History of treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed.).
• History of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening.
• History of treated diabetic gastric paresis.
• New York Heart Association Class III or IV heart failure regardless of therapy. Currently treated subjects who are stable at Class I or II are candidates for the study.
• History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 6 months prior to Screening.
• History of any hemoglobinopathy that may affect determination of glycosylated hemoglobin.
• History of infection with hepatitis B, hepatitis C, or human immunodeficiency virus.
• History of a psychiatric disorder that will affect ability to participate in the study.
• History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors.
• History of alcohol or substance abuse within the 2 years prior to Screening.
• Receipt of any investigational drug within the 30 days prior to Screening or a history of receipt of an investigational antidiabetic drug within the 3 months prior to Screening.
• Prior treatment in an investigational study of alogliptin.
• Excluded Medications:
• Treatment with antidiabetic agents other than insulin and metformin is not allowed within th