Conditions: Type 2 Diabetes
Keywords: Incretins colesevelam hepatobiliary circulation
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 38
Healthy volunteers: no

Brief summary:
The goal of this study was to determine the metabolic mechanism for a certain type medication's ability to lower blood sugar after a meal in Type 2 Diabetics, in order to develop a better understanding of it's potential role in the treatment of obesity.

Detailed description:
Welchol (colesevelam hydrochloride) is a bile acid sequestrant (BAS) recently approved by the FDA for glucose lowering in patients with type 2 diabetes mellitus. Four randomized, controlled clinical studies in subjects with type 2 diabetes have demonstrated significant treatment difference in HbA1c (-0.5%). Study durations ranged from 12-26 weeks of therapy. In diabetes clinical studies, a therapeutic response to colesevelam hydrochloride, as reflected by reduction in A1c was initially noted following 4-6 weeks of treatment and reached maximal or near-maximal effect after 12-18 weeks of treatment. Reductions in both fasting plasma glucose and postprandial concentrations have been demonstrated. Simple measures of insulin secretion and action have suggested that this is due to improved insulin action rather than improved insulin secretion. The mechanism by which bile acids interact with the key pathways regulating glucose concentrations is largely unknown. The investigators propose a randomized, double-blind, placebo controlled trial with a parallel-group design where subjects are randomized to receive colesevelam or matching placebo for a 12 week treatment period. A labeled mixed meal before and after treatment will be used to measure intestinal transit, postprandial and fasting glucose fluxes, insulin secretion and action as well as enteroendocrine secretion.

Arms:
arm 1: Treatment with colesevelam hydrochloride in addition to Metformin and Diet arm 2: Treatment with placebo in addition to Metformin and Diet

Interventions: intervention 1: Colesevelam intervention 2: Placebo intervention 3: Diet intervention 4: Metformin
Intervention descriptions: intervention 1: Colesevelam hydrochloride; three 625mg tablets taken orally twice per day before breakfast and before the evening meal over a 12-week treatment period. intervention 2: Three placebo tablets matching the active drug colesevelam in appearance, taken orally twice per day before breakfast and before the evening meal over a 12-week treatment period. intervention 3: Subjects were instructed to follow a weight maintenance diet (\~55% carbohydrate, 30% fat and 15% protein) for the 12 week study period. intervention 4: Subjects continued to take their pre-study therapeutic doses of metformin (Metformin 500mg tablets taken by mouth twice daily for a total daily dose of 1000 to 2000 mg) through the 12 week study period.

Protocol document: