title: Effects of colesevelam on glucose absorption and hepatic/peripheral insulin sensitivity in patients with type 2 diabetes mellitus.
abstract: OBJECTIVE
  Colesevelam lowers glucose and low-density lipoprotein cholesterol levels in patients with type 2 diabetes mellitus. This study examined the mechanisms by which colesevelam might affect glucose control.
  
  
  METHODS
  In this 12-week, randomized, double-blind, placebo-controlled study, subjects with type 2 diabetes and haemoglobin A(1c) (HbA(1c)) ≥7.5% on either stable diet and exercise or sulphonylurea therapy were randomized to colesevelam 3.75 g/day (n = 16) or placebo (n = 14). Hepatic/peripheral insulin sensitivity was evaluated at baseline and at week 12 by infusion of (3) H-labelled glucose followed by a 2-step hyperinsulinemic-euglycemic clamp. Two 75-g oral glucose tolerance tests (OGTTs) were conducted at baseline, one with and one without co-administration of colesevelam. A final OGTT was conducted at week 12. HbA(1c) and fasting plasma glucose (FPG) levels were evaluated pre- and post-treatment.
  
  
  RESULTS
  Treatment with colesevelam, compared to placebo, had no significant effects on basal endogenous glucose output, response to insulin or on maximal steady-state glucose disposal rate. At baseline, co-administration of colesevelam with oral glucose reduced total area under the glucose curve (AUC(g)) but not incremental AUC(g). At week 12, neither total AUC(g) nor incremental AUC(g) were changed from pre-treatment values in either group. Post-load insulin levels increased with colesevelam at 30 and 120 min, but these changes in total area under the insulin curve (AUC(i)) and incremental AUC(i) did not differ between groups. Both HbA(1c) and FPG improved with colesevelam, but treatment differences were not significant.
  
  
  CONCLUSIONS
  Colesevelam does not affect hepatic or peripheral insulin sensitivity and does not directly affect glucose absorption.
authors.affiliation: Section of Diabetes, Endocrinology and Metabolism, VA San Diego Healthcare System and University of California San Diego, San Diego, CA 92161, USA. rrhenry@vapop.ucsd.edu
authors.forename: R R
authors.initials: RR
authors.lastname: Henry
authors.forename: V R
authors.initials: VR
authors.lastname: Aroda
authors.forename: S
authors.initials: S
authors.lastname: Mudaliar
authors.forename: W T
authors.initials: WT
authors.lastname: Garvey
authors.forename: H S
authors.initials: HS
authors.lastname: Chou
authors.forename: M R
authors.initials: MR
authors.lastname: Jones
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000499:Allylamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000378:metabolism / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D008078:Cholesterol, LDL / Q000187:drug effects*; D000069472:Colesevelam Hydrochloride; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000378:metabolism / Q000627:therapeutic use*; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000499:Allylamine; D000924:Anticholesteremic Agents; D001786:Blood Glucose; D008078:Cholesterol, LDL; D000069472:Colesevelam Hydrochloride; D006442:Glycated Hemoglobin; D013453:Sulfonylurea Compounds