Effects of colesevelam on LDL-C, A1c and GLP-1 levels in patients with type 1 diabetes: a pilot randomized double-blind trial

Diabetes Obes Metab. 2011 Feb;13(2):137-43. doi: 10.1111/j.1463-1326.2010.01320.x.

Abstract

Aim: 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.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Allylamine / administration & dosage
  • Allylamine / analogs & derivatives*
  • Allylamine / pharmacology
  • Anticholesteremic Agents / administration & dosage*
  • Anticholesteremic Agents / pharmacology
  • Blood Glucose / drug effects
  • Cholesterol, LDL / drug effects*
  • Cholesterol, LDL / metabolism
  • Colesevelam Hydrochloride
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Double-Blind Method
  • Female
  • Glucagon-Like Peptide 1 / drug effects*
  • Glucagon-Like Peptide 1 / metabolism
  • Glycated Hemoglobin A / drug effects
  • Humans
  • Hyperlipidemias / drug therapy*
  • Male
  • Middle Aged
  • Patient Compliance
  • Pilot Projects
  • Young Adult

Substances

  • Anticholesteremic Agents
  • Blood Glucose
  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Allylamine
  • Glucagon-Like Peptide 1
  • Colesevelam Hydrochloride