Welchol as Add-on to Pioglitazone Therapy for Type 2 Diabetes Mellitus

Inclusion Criteria:

• Diagnosis of Type 2 Diabetes Mellitus.
• Inadequate glycemic control on a stable dose (at least 2 months prior to screening) of pioglitazone at 30 or 45 mg/day, with or without one or two other oral antidiabetic medications (metformin or a sulfonylurea. or DPP-IV inhibitor)
• A1C >= 7.5% and =< 9.5% at screening.
• Fasting plasma glucose =<240 mg/dL at randomization (Week0/Day 1).
• Male or female >= 18 years of age.
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception as detailed per-protocol.
• Fasting C-peptide level >0.5 ng/mL at screening.
• Clinically stable in regards to medical conditions other than type 2 diabetes.
• Concomitant medications are at stable doses for at least 30 days prior to enrollment, and are not anticipated to need adjustment during the study period.

Exclusion Criteria:

• History of Type 1 diabetes and/or history of ketoacidosis.
• History of bowel obstruction
• History of hypertriglyceridemia-induced pancreatitis
• Fasting serum triglyceride concentration >500 mg/dL
• History of dysphagia, swallowing disorders, gastroparesis, other gastrointestinal motility disorders, major gastrointestinal surgery
• History of insulin use >= 2 weeks duration during the previous 3 months or a total of >2 months insulin therapy at any time prior to screening
• Two or more fasting self-monitored blood glucose (SMBG) levels >240 mg/dL during the placebo lead-in period
• Body mass index >40 kg/m2 at screening
• Weight loss >3% in the 3 months prior to screening
• Treatment with bile acid sequestrants, including Welchol within 3 months prior to screening
• LDL level <60 mg/dL
• Female subject who is pregnant or breastfeeding
• SBP >= 180 mmHg and/or DBP >= 110 mmHg
• History of unstable angina, myocardial infarction, cerebrovascular accident, transient ischemic attack, or any revascularization within 6 months prior to screening
• History of malignancy, except subjects who have been disease-free for >10 years or whose malignancy was a basal or squamous cell skin carcinoma. Women with a history of cervical dysplasia (CIN2 or higher) should be excluded unless 2 consecutive normal cervical smears have subsequently been recorded prior to enrollment
• Known (or evidence of) infection with human immunodeficiency virus (HIV)
• History of alcohol or drug abuse within 1 year prior to screening
• History of untreated major psychiatric disorders that could inhibit abilities to comply with the protocol
• Any condition, lab abnormality or concomitant therapy which, in the opinion of the investigator, might pose a risk to the subject or make participation not in the subject's best interest
• Known or suspected allergy, hypersensitivity or intolerance to the excipients of the investigational study medication
• Participation in an interventional medical, surgical, or pharmaceutical study within 30 days prior to the screening visit
• A direct or familial relationship with the sponsor, investigator, or site personnel affiliated with the study.