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

Eligible subjects will be randomly assigned to treatment with either 6 tablets of Welchol or
6 tablets of placebo. The 6 tablets are to be taken in a single dose with dinner or 2
equally divided doses taken with lunch and dinner. Randomization will be stratified by oral
anti-diabetes drug therapy at the time of screening (pioglitazone monotherapy [30 mg or 45
mg] or pioglitazone combination therapy [metformin, SU, or DPP-4 inhibitor]).

During the trial, all subjects will be on a stable dose of pioglitazone monotherapy (30 mg
or 45 mg).

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.