Colesevelam hydrochloride for the treatment of type 2 diabetes mellitus.
BACKGROUND
Colesevelam hydrochloride is a bile acid sequestrant approved in January 2008 by the US Food and Drug Administration (FDA) for the treatment of adult patients with type 2 diabetes mellitus (DM) in combination with a sulfonylurea, metformin, and/or insulin therapy.


OBJECTIVE
The purpose of this article was to review the pharmacology, pharmacokinetics, efficacy, adverse effects and tolerability, drug-drug interactions, contraindications/precautions, dosage and administration, pharmacoeconomics, and the overall role of colesevelam in the management of adult patients with type 2 DM.


METHODS
A literature search using MEDLINE (1966-October 27, 2008), PubMed (1950-October 27, 2008), Science Direct (1994-October 27, 2008), Web of Science (1980-October 27, 2008), American Diabetes Association Scientific Abstracts (2004-2008), and International Pharmaceutical Abstracts (1970-October 27, 2008) was performed using the term colesevelam. English-language, original research and review articles were examined, and citations from these articles were assessed. Manufacturer prescribing information and the FDA review of the new drug application for colesevelam were also examined.


RESULTS
Colesevelam is a hydrophilic, water-insoluble polymer, with negligible absorption and systemic distribution, that is excreted primarily in the feces. Through a mechanism still under investigation, colesevelam effectively lowers glycosylated hemoglobin (HbA(1c)) when used in combination with a sulfonylurea, metformin, and/or insulin therapy. Three completed, published Phase III clinical trials investigating colesevelam for the treatment of type 2 DM were evaluated for information, data, and conclusions. At dosing of 1.875 g BID or 3.75 g once daily in combination with one of the aforementioned agents versus placebo, reductions in HbA(1c) in all 3 Phase III clinical trials of colesevelam ranged from 0.5% to 0.7% (P < 0.02). In clinical trials, colesevelam was well tolerated, with hypoglycemia occurring in approximately 3% of studied patients.


CONCLUSIONS
When used in combination with a sulfonylurea, metformin, and/or insulin therapy, colesevelam has been reported to significantly reduce HbA(1c) in adult patients with type 2 DM. Colesevelam's role in the management of type 2 DM remains undefined, however; further investigation into its mechanism of action and long-term efficacy and safety should be performed.
Sonnett
Travis E
TE
Department of Pharmacotherapy, College of Pharmacy, Washington State University, Pullman, Washington 99164-6510, USA. tsonnett@wsu.edu
Levien
Terri L
TL
Neumiller
Joshua J
JJ
Gates
Brian J
BJ
Setter
Stephen M
SM
D000328:Adult; D000499:Allylamine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000191:economics / Q000493:pharmacokinetics; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics; D002986:Clinical Trials as Topic; D000069472:Colesevelam Hydrochloride; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000191:economics / Q000503:physiopathology; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage
D000499:Allylamine; D000924:Anticholesteremic Agents; D000069472:Colesevelam Hydrochloride; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents