title: Initial combination therapy with metformin plus colesevelam improves lipoprotein particles in patients with early type 2 diabetes mellitus.
abstract: BACKGROUND
  The bile acid sequestrant colesevelam has been shown to significantly reduce low-density lipoprotein particle concentration (LDL-P) in adults with primary hyperlipidemia or type 2 diabetes mellitus (T2DM).
  
  
  OBJECTIVE
  To assess the effect of initial combination therapy with metformin plus colesevelam on lipoprotein particles in patients with T2DM (secondary efficacy variables).
  
  
  METHODS
  This 16-week, randomized, double-blind, placebo-controlled study enrolled drug-naïve adults with T2DM, glycated hemoglobin 6.5%-10.0%, low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL, and triglycerides <500 mg/dL. Patients were randomized 1:1 to either open-label metformin (titrated to 1700 mg/day) plus double-blind colesevelam 3.75 g/day or open-label metformin plus double-blind placebo.
  
  
  RESULTS
  In total, 286 patients were randomized (metformin plus colesevelam [n = 145]; metformin plus placebo [n = 141]). Compared with metformin plus placebo, the combination of metformin plus colesevelam significantly reduced LDL-C (mean treatment difference: -16.3%), total cholesterol (-6.1%), non-high-density lipoprotein cholesterol (-8.3%), and apolipoprotein (apo) B (-8.0%) and significantly increased triglycerides (median treatment difference: 18.6%) and apoA-I (mean treatment difference: 4.4%; all P < .001). Metformin plus colesevelam significantly reduced total LDL-P (mean treatment difference: absolute change -186 nmol/L [percent change -11.7%]; both P < .0001), largely attributable to a reduction in small LDL-P, and increased total very-low-density lipoprotein particle concentration (mean treatment difference: absolute change 6 nmol/L; P = .03 [percent change 8.3%; P = .06]) and total high-density lipoprotein particle concentration (1.0 μmol/L; P = .03 [4.5%; P = .01]) versus metformin plus placebo.
  
  
  CONCLUSIONS
  Initial combination therapy with metformin plus colesevelam improved the atherogenic lipoprotein profile of patients with early T2DM by significantly reducing LDL-P. ClinicalTrials.gov identifier: NCT00570739.
authors: Division of Endocrinology, Diabetes and Metabolism, University of Miami Miller School of Medicine, Miami, FL 33136, USA. rgoldber@med.miami.edu
authors: Ronald B
authors: RB
authors: Goldberg
authors: Robert S
authors: RS
authors: Rosenson
authors: Eric
authors: E
authors: Hernandez-Triana
authors: Soamnauth
authors: S
authors: Misir
authors: Michael R
authors: MR
authors: Jones
mesh_terms: D000328:Adult; D000499:Allylamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D000069472:Colesevelam Hydrochloride; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D015990:Placebo Effect; D014280:Triglycerides / Q000097:blood
chemical_list: D000499:Allylamine; D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000069472:Colesevelam Hydrochloride; D006442:Glycated Hemoglobin; D008077:Lipoproteins, LDL; D008687:Metformin; D014280:Triglycerides