Glycemic Effect of Colesevelam HCl (Welchol) in Patients With Type 2 Diabetes

Phase 2

Completed

Brief Summary: The purpose of this study is to obtain continuous glucose monitoring (CGM) data from individuals taking Welchol compared to placebo. The CGM data will determine the effect on glucose control of adding Welchol to an anti-diabetic medication regimen.

Detailed Description: To understand the effect of the addition of colesevelam HCl to oral agent therapy in individuals with type 2 diabetes on glycemic control by utilizing a novel technology, continuous glucose monitoring with ambulatory glucose profile analysis. To date there are no studies of this compound that have employed continuous glucose monitoring (CGM) with ambulatory glucose profile (AGP) analysis to obtain data that will detail the diurnal glucose patterns associated with this therapy. We plan to employ CGM at critical points throughout the study. AGP analysis will enable rapid assessment of the clinical status of the subject. Using statistically stable estimates of hourly values represented by five percentile curves AGP depicts glucose exposure, variability and stability. Previously, we have used AGP analysis to characterize glucose perturbations in individuals ranging from normal glucose tolerance to overt type 2 diabetes.

Recruitment & Eligibility

Inclusion Criteria

Male or female subjects ≥18 and ≤75 years of age
Clinical diagnosis of type 2 diabetes
Currently treated with metformin, a sulfonylurea, or combination metformin/sulfonylurea; stable dose for ≥3 months
HbA1c of 7.0-9.0% inclusive
If taking lipid lowering medications, stable dose for >30 days

Exclusion Criteria

Taken oral or injected prednisone or cortisone medications in the previous 30 days. (Topical or inhaled steroids will not be considered excluded medications.)
Current use of insulin or TZD's, or incretins
LDL <70 mg/dL
Serum triglycerides >500 mg/dL
History of hypertriglyceridemia-induced pancreatitis
History of gastrointestinal disorder such as dysphagia, swallowing disorder, intestinal motility disorder or prior bowel obstruction
History or presence of any severe medical or psychological condition or chronic conditions/infections that in the opinion of the Investigator would compromise the subject's safety or successful participation in the study
Unable to follow the study protocol
Unable to speak, read and write in English
Pregnant, planning to become pregnant, breast feeding

Arm && Interventions

Group	Intervention	Description
Placebo then Welchol	colesevelam HCl	Placebo taken for 12 weeks at evening meal, and then crossover to 3.75 grams of colesevelam HCl taken at evening meal fro 12 weeks.
Welchol then Placebo	colesevelam HCl	3.75 grams of colesevelam HCl (Welchol) at evening meal for 12 weeks, and then crossover to placebo at evening meal for 12 weeks.
Welchol then Placebo	placebo	3.75 grams of colesevelam HCl (Welchol) at evening meal for 12 weeks, and then crossover to placebo at evening meal for 12 weeks.
Placebo then Welchol	placebo	Placebo taken for 12 weeks at evening meal, and then crossover to 3.75 grams of colesevelam HCl taken at evening meal fro 12 weeks.

Primary Outcome Measures

Name	Time	Method
Hypoglycemia Percentage of Time <70 mg/dL Average by Group	2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2.	Ambulatory glucose profile (AGP) reports were examined for the changes in the incidence of hypoglycemia (CGM\<70 mg/dL)
Total Norm AUC Average by Group (Normalized)	2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2.	Double Blinded CGM used for 2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2.
Sleep Norm AUC Average by Group (Normalized)	2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2.	Overnight glucose captured by CGM.
Wake Norm AUC Average by Group (Normalized)	2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2.	Wake glucose captured by continuous glucose monitoring (CGM).