The effect of colesevelam hydrochloride on insulin sensitivity and secretion in patients with type 2 diabetes: a pilot study

Metab Syndr Relat Disord. 2010 Apr;8(2):179-88. doi: 10.1089/met.2009.0049.


Background: This study evaluated the effect of colesevelam hydrochloride on insulin sensitivity, potential binding to glucose, and chronic effect(s) on fasting and postprandial glucose and insulin in patients with type 2 diabetes mellitus.

Methods: Patients meeting inclusion criteria were withdrawn from all antidiabetes agents for 2 weeks and randomized to colesevelam 3.75 grams/day (n = 17) or placebo (n = 18) for 8 weeks. Hyperinsulinemic-euglycemic clamp studies were performed at baseline (week -1) and weeks 2 and 8. A meal tolerance test was conducted at weeks -1, 0, 2, and 8. The meal tolerance test and study drug were coadministered at week 0 to assess the direct effect of colesevelam on glucose absorption.

Results: Insulin sensitivity as measured by the insulin clamp method did not change, but the Matsuda Index, a measure of whole-body insulin sensitivity calculated from postmeal tolerance test glucose and insulin levels, increased significantly within the colesevelam group from baseline to week 8 with last observation carried forward (P = 0.020). The postprandial area under the curve for glucose decreased with colesevelam versus placebo at weeks 2 and 8 with last observation carried forward (P = 0.012 and P = 0.061, respectively); the area under the curve for insulin did not decrease in concert with the decrease in area under the curve for glucose at week 2 (P = 0.585). Colesevelam had no effect on postmeal tolerance test glucose levels at week 0.

Conclusions: These results suggest that colesevelam has no effect on peripheral insulin sensitivity or glucose absorption, but may improve glucose control by improving whole-body insulin sensitivity, although not by an acute effect on glucose absorption. CLINICAL TRIAL IDENTIFIER: NCT00361153.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Algorithms
  • Allylamine / adverse effects
  • Allylamine / analogs & derivatives*
  • Allylamine / pharmacology
  • Allylamine / therapeutic use
  • Anticholesteremic Agents / adverse effects
  • Anticholesteremic Agents / pharmacology
  • Anticholesteremic Agents / therapeutic use
  • Colesevelam Hydrochloride
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Double-Blind Method
  • Female
  • Glucose Clamp Technique
  • Humans
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Resistance*
  • Insulin Secretion
  • Male
  • Middle Aged
  • Pilot Projects
  • Placebos
  • Postprandial Period / drug effects


  • Anticholesteremic Agents
  • Insulin
  • Placebos
  • Allylamine
  • Colesevelam Hydrochloride

Associated data