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

Abstract

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Patients meeting inclusion criteria were withdrawn from all antidiabetes agents for 2 weeks and randomized to colesevelam 3.75 grams/day (n = 17) or placebo (n = 18) for 8 weeks.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.

• Authors: Sherwyn L Schwartz, Yu-Ling Lai, Jianbo Xu, Stacey L Abby, Soamnauth Misir, Michael R Jones, Sukumar Nagendran
• Journal: Metabolic syndrome and related disorders (Metab Syndr Relat Disord) Vol. 8 Issue 2 Pg. 179-88 (Apr 2010) ISSN: 1557-8518 [Electronic] United States
• PMID: 20059361 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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