The Effects of Co-admin of Colesevelam and Sitagliptin on Glucose Metabolism in Subjects With Type 2 Diabetes Mellitus

The Effects of Co-administration of Colesevelam and Sitagliptin on Glucose Metabolism in Patients With Type 2 Diabetes

This study will assess the effects of colesevelam, alone or in combination with sitagliptin, on glucose metabolism in subjects with T2DM inadequately controlled by diet and exercise

The hypothesis is that co-administrationof colesevelam plus sitagliptin results in a greater reduction in HbA1c compared to colesevelam HCl treatment by

1. improving the effects of colesevelam on fasting glucose metabolism
2. improving the effects of colsevelam on postprandial glucose metabolism

Inclusion Criteria:

• Male or Female
• Females of childbearing potential are on approved birth control method
• Negative pregnancy testing for females of childbearing potential
• Previously diagnosed or newly diagnosed with T2DM drug naïve subjects
• HbA1c: 6.7-10%
• Age 18 - 80 years
• BMI ≥ 18.5 kg/m2 and ≤ 40 kg/m2
• Fasting serum glucose < 300 mg/dL
• Normal liver function, normal thyroid function, no history of liver, biliary or intestinal disease
• Normal TSH
• On stable diet and exercise routine for at least 4 weeks prior to screening
• Has had a stable weight (+/-5%) for ≥3 months before screening

Exclusion Criteria:

• A history of type 1 diabetes mellitus or history of diabetic ketoacidosis
• History of chronic (required daily for > 2 months) use of insulin therapy
• Treatment with blood pressure lowering therapy that has not been stable for three months before screening
• Treatment with lipid lowering medication other than statins
• Treatment with statins that has not been stable for three months before screening
• Treatment with a DPP-4 inhibitor or and GLP1 agonists at any time
• Treatment with a thiazolidinedione (TZD) within the last 6 months of screening
• History of an allergic or toxic reaction to sitagliptin or colesevelam
• History of dysphagia, swallowing disorders, bowel obstruction, intestinal motility disorder, and gastrointestinal disorders
• History of major gastrointestinal surgery
• History of kidney problems
• Fasting plasma triglycerides > 300 mg/dL
• Serum LDL-C <60 mg/dL
• Positive toxicology test
• Known hypersensitivity to colesevelam HCl or sitagliptin.
• Any contraindications to a study medication (colesevelam HCl or sitagliptin).