title: Rationale and design of a prospective clinical trial program to evaluate the glucose-lowering effects of colesevelam HCl in patients with type 2 diabetes mellitus.
abstract: BACKGROUND
  Dyslipidemia and type 2 diabetes mellitus (T2DM) increase atherosclerotic coronary heart disease (CHD) risk. In patients with T2DM, improving lipid parameters reduces CHD risk, while optimizing glucose levels reduces microvascular complications and, possibly, macrovascular disease such as CHD. Unfortunately, many patients with T2DM do not achieve either lipid or glucose treatment targets.
  
  
  OBJECTIVE
  Colesevelam HCl is a specifically engineered bile-acid sequestrant (BAS) indicated to reduce elevated low-density lipoprotein cholesterol concentrations. Earlier studies have demonstrated that BAS not only reduce cholesterol levels, but also lower glucose levels in patients with T2DM. These findings have prompted a robust, prospective phase 3 clinical trial program to further evaluate the safety and tolerability of colesevelam HCl when added to T2DM patients previously treated with metformin, insulin or a sulfonylurea. A limitation of these clinical trials is that none of them assessed colesevelam HCl monotherapy, nor directly compared the glucose-lowering effects of colesevelam HCl to established oral antidiabetes drugs. Nonetheless, this clinical trial program will better determine whether a single agent added to existing diabetes therapy can improve both lipid and glucose parameters in T2DM, which may allow more patients to achieve lipid and glucose treatment targets.
  
  
  CONCLUSIONS
  This phase 3 clinical trial program will evaluate colesevelam's glucose-lowering effects in patients with T2DM. In addition, based upon a review of the relevant medical literature through an online electronic PubMed search (without restriction to date other than otherwise occurs through PubMed), potential mechanisms as to how BAS may lower glucose levels are discussed.
authors.affiliation: Louisville Metabolic and Atherosclerosis Research Center Inc., Louisville, KY 40213,USA. hbaysmd@aol.com
authors.forename: Harold E
authors.initials: HE
authors.lastname: Bays
authors.forename: David E
authors.initials: DE
authors.lastname: Cohen
mesh_terms: D000328:Adult; D000368:Aged; D000499:Allylamine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001647:Bile Acids and Salts / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects*; D000069472:Colesevelam Hydrochloride; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D016730:Program Development; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D001786:Blood Glucose; D018160:Receptors, Cytoplasmic and Nuclear; D000499:Allylamine; D005947:Glucose; D000069472:Colesevelam Hydrochloride