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

8 Citationer (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.

OriginalsprogEngelsk
TidsskriftExpert Opinion on Drug Discovery
Vol/bind13
Udgave nummer12
Sider (fra-til)1161-1167
Antal sider8
ISSN1746-0441
DOI
StatusUdgivet - okt. 2018

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