title: Effects of colesevelam on LDL-C, A1c and GLP-1 levels in patients with type 1 diabetes: a pilot randomized double-blind trial.
abstract: OBJECTIVE
  colesevelam is indicated to lower low density lipoprotein cholesterol (LDL-C) in hyperlipidaemia and improve glycaemic control in adults with type 2 diabetes. This short-term pilot study evaluates its effects in type 1 diabetes.
  
  
  METHODS
  this double-blind, randomized, investigator-initiated, single-centred, 12-week pilot study evaluated 40 adults (age = 36.4 ± 9.4 years) with type 1 diabetes (duration = 20.4 ± 8.5 years) and hyperlipidaemia. It was powered to show a treatment difference of >10% LDL-C reduction. Subjects received 3.75 g/day colesevelam (n = 20) or placebo (n = 20) for 12 weeks. LDL-C and haemoglobin A1c (A1c) levels were assessed at screening (week 2), baseline (week 0) and every 4 weeks throughout the treatment duration. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) levels were measured during 4-h meal (Boost Plus, Nestle HealthCare Nutrition Inc., Florham Park, New Jersey, USA) challenge tests (MCT) at baseline and 12 weeks.
  
  
  RESULTS
  colesevelam treatment resulted in a significant reduction in LDL-C values at 4 weeks [-12.1% (95% CI: -20.1 to -4.1), p = 0.004] which was sustained for the study duration (p = 0.005 at 12 weeks). The treatment group also showed a significant change in A1c from baseline at week 4; however, this was not significant for the study duration. There was a significant median increase in GLP-1 levels during the first 2 h of the baseline MCT in the treated group but no difference at 12 weeks.
  
  
  CONCLUSIONS
  during this short-term pilot study, colesevelam treatment effectively lowered LDL-C in patients with type 1 diabetes. Improvements in A1c seen at week 4 were not sustained. Effects on glycaemic control in subjects with type 1 diabetes may be related to a postprandial rise in GLP-1 levels and require further clinical study.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Aurora, CO 80045, USA. satish.garg@ucdenver.edu
authors.forename: S K
authors.initials: SK
authors.lastname: Garg
authors.forename: P J
authors.initials: PJ
authors.lastname: Ritchie
authors.forename: E G
authors.initials: EG
authors.lastname: Moser
authors.forename: J K
authors.initials: JK
authors.lastname: Snell-Bergeon
authors.forename: B J
authors.initials: BJ
authors.lastname: Freson
authors.forename: R M
authors.initials: RM
authors.lastname: Hazenfield
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000499:Allylamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D008078:Cholesterol, LDL / Q000187:drug effects* / Q000378:metabolism; D000069472:Colesevelam Hydrochloride; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000187:drug effects* / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010865:Pilot Projects; D055815:Young Adult
chemical_list: D000499:Allylamine; D000924:Anticholesteremic Agents; D001786:Blood Glucose; D008078:Cholesterol, LDL; D000069472:Colesevelam Hydrochloride; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin