Preclinical discovery and development of colesevelam for the treatment of type 2 diabetes

Henriette Holst Nerild, Mikkel Bring Christensen*, Filip Krag Knop, Andreas Brønden

*Corresponding author for this work
5 Citations (Scopus)

Abstract

Introduction: Type 2 diabetes (T2D) is a major global health challenge associated with increased cardiovascular morbidity and mortality. Intervention strategies managing multiple risk factors (hyperglycemia, hypertension and dyslipidemia) in patients with T2D can reduce the risk of cardiovascular disease by ~50%. Areas covered: Herein, the authors provide an update on the development and clinical potential of colesevelam as a glucose-lowering drug in T2D. Furthermore, they outline the pharmacokinetics, pharmacodynamics, and the clinical efficacy and safety data from the studies carried out to obtain market authorization for colesevelam. Expert opinion: Four phase III clinical trials provide evidence that colesevelam, as a monotherapy and add-on to various background glucose-lowering treatments, confers placebo-corrected reductions in HbA1c of ~5 mmol/mol. In addition, colesevelam reduces low-density lipoprotein (LDL) cholesterol and total cholesterol. Some antidiabetic agents seem superior to colesevelam in terms of clinical efficiency (HbA1c lowering), tolerability/convenience, and price. Nonetheless, colesevelam offers a clinically relevant combination of HbA1c- and LDL-lowering that in selected patients could be relevant as add-on treatment to other glucose-lowering drugs and a statin. Potential patients include those with renal impairment, and patients that are close to reaching their lipid and glycemic treatment goals but need further LDL and HbA1c reductions.

Original languageEnglish
JournalExpert Opinion on Drug Discovery
Volume13
Issue number12
Pages (from-to)1161-1167
Number of pages7
ISSN1746-0441
DOIs
Publication statusPublished - 2018

Keywords

  • Bile acid
  • bile acid sequestrant
  • colesevelam
  • glucose metabolism
  • type 2 diabetes

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