Efficacy of Alogliptin and Pioglitazone in Subjects With Type 2 Diabetes Mellitus

Inclusion Criteria

• Has a historical diagnosis of type 2 diabetes mellitus.
• Meets one of the following:
• Has been inadequately controlled (HbA1c between 7% and 10%, inclusive) on a stable dose of greater than or equal to 1500 mg (or maximum tolerated dose) of metformin and 30 mg of pioglitazone
• Has been inadequately controlled (as defined by an HbA1c ≥7.5%) on a combination therapy including metformin and another oral antidiabetic agent (ie, sulfonylureas, rosiglitazone maleate, or pioglitazone 15 mg, etc). Subjects on a combination therapy that included a DPP-4 inhibitor were excluded.
• No treatment with antidiabetic agents other than metformin and pioglitazone.
• Body mass index greater than or equal to 23 kg/m^2 and less than or equal to 45 kg/m^2.
• Fasting plasma C-peptide concentration greater than or equal to 0.8 ng/mL.
• Systolic blood pressure less than 160 mmHg and diastolic pressure less than 100 mmHg.
• Hemoglobin greater than or equal to 12 g/dL for males and greater than or equal to 10 g/dL for females.
• Alanine aminotransferase less than or equal to 2.5 x upper limit of normal.
• Serum creatinine less than 1.5 mg/dL for males and less than 1.4 mg/dL for females.
• Thyroid-stimulating hormone level less than or equal to the upper limit of normal range and the patient is clinically euthyroid.
• Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
• Able and willing to monitor their own blood glucose concentrations with a home glucose monitor.
• No major illness or debility that in the investigator's opinion prohibits the patient from completing the study.

Exclusion Criteria

• Urine albumin/creatinine ratio of greater than 1000 μg/mg.
• 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 bladder cancer.
• History of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening.
• Patients with unexplained microscopic hematuria of greater than +1, confirmed by repeat testing.
• History of treated diabetic gastroparesis.
• History of gastric bypass surgery.
• New York Heart Association Class I-IV heart failure regardless of therapy.
• 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 the patient's 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 abuse 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.
• Hypersensitive to pioglitazone HCl, metformin, alogliptin or other excipients.
• The patient has donated more than 400 mL of blood within the 90 days prior to Screening and Pre-Screening, if applicable.