title: An economic evaluation of colesevelam when added to metformin-, insulin- or sulfonylurea-based therapies in patients with uncontrolled type 2 diabetes mellitus.
abstract: BACKGROUND
  Several early studies demonstrated that bile acid sequestrants were useful for lowering lipid levels in patients with hypercholesterolaemia and may also be useful for lowering glucose levels in patients with type 2 diabetes mellitus (T2DM) uncontrolled on existing treatment (metformin-, insulin- or sulfonylurea-based therapies).
  
  
  OBJECTIVE
  This study modelled efficacy and safety data from the three clinical trials to evaluate the cost effectiveness to US Managed Care Organizations of add-on treatment with colesevelam for reducing diabetes-related complications.
  
  
  METHODS
  Three randomized controlled trials in patients with T2DM and one in hyperlipidaemia established that colesevelam lowered both glycaemic and lipid parameters in adult patients participating in the studies. The validated 'diabetic risk equation' (DRE) and the 'LIPID cardiovascular risk equation' (LCRE) were used to translate the observed clinical benefits (surrogate markers related to T2DM [glycosylated haemoglobin {HbA(1c)} and fasting plasma glucose] and cardiovascular disease [low-density lipoprotein cholesterol {LDL-C}]). Performing an appropriate economic evaluation required the use of both the DRE and the LCRE. These equations parameterize the clinical efficacy measures as continuous, facilitating their application to clinical trial results as well as the replication of other well established epidemiological data. Tobit regressions were applied to a large commercially available managed care administrative claims database (2000-6), Integrated Health Care Services (IHCS), to evaluate the incremental costs associated with each type of diabetic complication. Costs were inflated to 2010 values using the Healthcare Consumer Price Index, while second- and third-year cost savings were discounted at 5% to the current year. Bootstrap sampling with 5000 samples of 100 patients per cohort was conducted, varying the number of events avoided as well as their associated cost.
  
  
  RESULTS
  With established metformin-, insulin- or sulfonylurea-based therapies, the addition of colesevelam significantly reduced HbA(1c) by approximately 0.5% (p < 0.001) in all three studies. In addition, colesevelam reduced placebo-adjusted LDL-C by 12.8-16.7% (p < 0.001). Using the DRE and LCRE equations, the total savings from reductions in diabetes-related and cardiovascular events were $US3543, $US4074 and $US3855 for colesevelam added to metformin-, insulin- and sulfonylurea-based regimens in patients with normal lipid levels. After subtracting the cost of colesevelam, first-year savings were $US1326, $US1852 and $US1629 in the metformin, insulin and sulfonylurea studies, respectively, for patients with raised lipid levels.
  
  
  CONCLUSIONS
  In adult patients with T2DM, the addition of colesevelam to metformin-, insulin- or sulfonylurea-based therapies significantly improves glycaemic control while also reducing LDL-C, and these improvements could translate into substantial cost reductions due to reductions in the rates of diabetes-related and cardiovascular complications.
authors.affiliation: Global Health Economics & Outcomes Research, Inc., Summit, New Jersey 07901, USA. rsimons@globalhealtheconomics.com
authors.forename: W Robert
authors.initials: WR
authors.lastname: Simons
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hagan
mesh_terms: D000328:Adult; D000368:Aged; D000499:Allylamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000191:economics / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000191:economics / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood; D000069472:Colesevelam Hydrochloride; D003362:Cost-Benefit Analysis / Q000379:methods; D016208:Databases, Factual; D048909:Diabetes Complications / Q000191:economics / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000191:economics*; D004359:Drug Therapy, Combination / Q000191:economics / Q000379:methods; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D017048:Health Care Costs; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy; D007328:Insulin / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*; D008875:Middle Aged; D018803:Models, Economic; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States
chemical_list: D000499:Allylamine; D008078:Cholesterol, LDL; D000069472:Colesevelam Hydrochloride; D006442:Glycated Hemoglobin; D007328:Insulin; D008687:Metformin; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human
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