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

Study Overview
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Brief Summary
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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

Detailed Description
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The hypothesis is that co-administrationof colesevelam plus sitagliptin results in a greater reduction in HbA1c compared to colesevelam HCl treatment by improving the effects of colesevelam on fasting glucose metabolism improving the effects of colsevelam on postprandial glucose metabolism

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

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Colesevelam HCl
* Drug: Sitagliptin


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Colesevelam HCl: 3 tablets, 2x/day<br>Subjects will be given 3.75 g/day. Subjects will be given 3 tablets (625mg each) with breakfast and 3 tablets (625mg) with dinner for 12 weeks. | Drug: Colesevelam HCl<br>* Subjects will be given 3.75 g/day. Subjects will be given 3 tablets (625mg each) with breakfast and 3 tablets (625mg) with dinner for 12 weeks.<br>* Other names: Welchol;|
| Active Comparator: Colesevelam plus Sitagliptin<br>Colesevelam: Subjects will be given 3.75 g/day. Subjects will be given 3 tablets (625mg each) with breakfast and 3 tablets (625mg) with dinner for 12 weeks. Sitagliptin: Subjects will be given 100mg/day. Subjects will be given 1 tablet (100mg) with breakfast for 12 weeks. | Drug: Colesevelam HCl<br>* Subjects will be given 3.75 g/day. Subjects will be given 3 tablets (625mg each) with breakfast and 3 tablets (625mg) with dinner for 12 weeks.<br>* Other names: Welchol;Drug: Sitagliptin<br>* Subjects will be given 100mg/day. Subjects will be given 1 tablet (100mg) with breakfast for 12 weeks.<br>* Other names: Januvia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin A1C | Change from baseline in hemoglobin A1C after 12 weeks of colesevelam or colesevelam plus sitagliptin treatments | Baseline and 12 weeks | 
| Fasting Plasma Glucose | Change from baseline in fasting plasma glucose concentrations after 12 weeks of colesevelam or colesevelam plus sitagliptin treatments. | Baseline and 12 weeks | 
| Fasting Endogenous Glucose Production | Change from baseline in fasting endogenous glucose production after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment | baseline and 12 weeks | 
| Fasting Gluconeogenesis | Change from baseline in fasting gluconeogenesis after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment | baseline and 12 weeks | 
| Fasting Glycogenolysis | Change from baseline in fasting glycogenolysis after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment | baseline and 12 weeks | 
| Fasting Plasma Glucose Clearance | Change from baseline in fasting plasma glucose clearance after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments. | baseline and 12 weeks | 
| Appearance Rate of Oral Glucose | Change from baseline in appearance rate of oral glucose after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments | baseline and 12 weeks | 
| Postprandial Endogenous Glucose Production | Change from baseline in postprandial endogenous glucose production after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments Mean value was calculated using all results measured between 10 and 300 min post meal. | baseline and 12 weeks | 
| Postprandial Rate of Total Glucose Disposal Area Under the Curve (AUC) | Change from baseline in postprandial rate of total glucose disposal (AUC) after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments AUC was calculated by the trapezoid method using all results measured between 0 and 300 min during the meal tolerance test. | baseline and 12 weeks | 
| Whole-body Glycolytic Disposal of Oral Glucose | Change in baseline in whole-body glycolytic disposal of oral glucose after 12 weeks of colesevelam alone or colesevelam plus glucose treatments | baseline and 12 weeks | 
| Postprandial Glucose (AUC) | Comparison between baseline and 12 weeks values of postrandial glucose (AUC). | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Plasma C-peptide | To evaluate the effect of treatments on plamsa C-peptide concentrations. | Baseline and 12 weeks | 
| Fasting Plamsa Glucagon | To evaluate the effect of treatments on plasma glucagon concentrations. | Baseline and 12 weeks | 
| Fasting Active Plasma Glucagon Like-Peptide 1 (GLP-1) | To evaluate the effect of treatments on plasma GLP-1 concentrations. | Baseline and 12 weeks | 
| Fasting Plasma Total Glucose-dependent Insulinotropic Peptide (GIP) | To evaluate the effect of treatments on plasma Glucose-dependent Insulinotropic Peptide (GIP) concentrations. | Baseline and 12 weeks | 
| Fasting Insulin | To evaluate the effect of treatments on fasting insulin concentrations | Baseline and 12 weeks | 
| Postprandial Insulin (AUC) | To evaluate the effect of treatments on postprandial insulin (AUC) | Baseline and 12 weeks | 
| Postprandial C-peptide (AUC) | To evaluate the effect of treatments on postprandial C-peptide (AUC) | Baseline and 12 weeks | 
| Postprandial Active GLP-1 (AUC) | To evaluate the effects of treatments on postprandial active GLP-1 (AUC) | Baseline and 12 weeks | 
| Postprandial Total GIP (AUC) | To evaluate the effects of treatment on postprandial total GIP (AUC) | Baseline and 12 weeks | 
| Postprandial Glucagon (AUC) | To evaluate the effects of treatment on postprandial glucagon (AUC) | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colesevelam, type 2 diabetes, sitagliptin, glucose metabolism