title: Colesevelam hydrochloride added to background metformin therapy in patients with type 2 diabetes mellitus: a pooled analysis from 3 clinical studies.
abstract: OBJECTIVE
  To evaluate the glucose- and lipid-altering efficacy of colesevelam hydrochloride (HCl) when added to background metformin therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  This post hoc analysis included patients with T2DM from 3 randomized, double-blind, placebo-controlled pivotal studies who received metformin as part of their background antidiabetes therapy. In the pivotal studies, patients with T2DM were randomly assigned to receive colesevelam HCl (3.75 g/d) or placebo added to existing metformin (26 weeks), sulfonylurea (26 weeks), or insulin (16 weeks) monotherapy or combination therapy, wherein the combination therapies may have included metformin.
  
  
  RESULTS
  In this pooled analysis of 696 patients with T2DM who were receiving metformin monotherapy or metformin combined with other antidiabetes therapies, 355 were randomly assigned to receive colesevelam HCl and 341 to receive placebo. In comparison with placebo, colesevelam HCl significantly reduced hemoglobin A1c (A1C) and fasting plasma glucose (mean treatment difference: -0.50% and -15.7 mg/dL, respectively; P<.001 for both), as well as significantly reduced levels of low-density lipoprotein cholesterol (LDL-C; mean treatment difference: -16.5%), total cholesterol (TC; -5.8%), non-high-density lipoprotein cholesterol (non-HDL-C; -8.2%), and apolipoprotein (apo) B (-7.6%) (P<.0001 for all). Median triglyceride levels were increased with colesevelam HCl (median treatment difference: +12.8%; P<.0001). In comparison with placebo, colesevelam HCl significantly increased apo A-I (mean treatment difference: +3.3%; P<.0001), whereas the mean increase in HDL-C with colesevelam HCl was not significant. Colesevelam HCl therapy was generally well tolerated.
  
  
  CONCLUSIONS
  When added to metformin-including therapy, colesevelam HCl significantly reduced A1C and fasting glucose, as well as levels of LDL-C, TC, non-HDL-C, and apo B in patients with inadequately controlled T2DM.
authors.affiliation: Louisville Metabolic and Atherosclerosis Research Center, Inc., Louisville, Kentucky 40213, USA. HBaysMD@aol.com
authors.forename: Harold E
authors.initials: HE
authors.lastname: Bays
mesh_terms: D000368:Aged; D000499:Allylamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D000069472:Colesevelam Hydrochloride; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006937:Hypercholesterolemia / Q000517:prevention & control*; D006943:Hyperglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D057194:Intention to Treat Analysis; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010352:Patient Dropouts; D013453:Sulfonylurea Compounds / Q000627:therapeutic use
chemical_list: D000499:Allylamine; D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D002784:Cholesterol; D008078:Cholesterol, LDL; D000069472:Colesevelam Hydrochloride; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human