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 METHODS: Patients meeting inclusion criteria were withdrawn from all antidiabetes agents for 2 weeks and randomized to colesevelam 3.75 grams/day (n = 17) or placebo (n = 18) for 8 weeks.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.
RCT Entities:
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 METHODS:Patients meeting inclusion criteria were withdrawn from all antidiabetes agents for 2 weeks and randomized to colesevelam 3.75 grams/day (n = 17) or placebo (n = 18) for 8 weeks.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: C Beysen; E J Murphy; K Deines; M Chan; E Tsang; A Glass; S M Turner; J Protasio; T Riiff; M K Hellerstein Journal: Diabetologia Date: 2011-12-02 Impact factor: 10.122