title: Initial combination therapy with metformin and colesevelam for achievement of glycemic and lipid goals in early type 2 diabetes.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of initial combination therapy with metformin plus colesevelam in patients with early type 2 diabetes.
  
  
  METHODS
  In this 16-week, randomized, double-blind, placebo-controlled study, adults with type 2 diabetes (hemoglobin A1c [A1C] values of 6.5% to 10.0%) and hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] levels > or =100 mg/dL) were randomly assigned (1:1) to colesevelam (3.75 g/d) or placebo in combination with open-label metformin (850 mg/d; uptitrated at week 2 to 1,700 mg/d). The primary efficacy evaluation was change in A1C from baseline to study end (week 16 with last observation carried forward).
  
  
  RESULTS
  In total, 286 patients were randomized: metformin/colesevelam (n = 145) or metformin/placebo (n = 141). Mean A1C was reduced by 1.1% with metformin/colesevelam (from 7.8% at baseline to 6.6% at study end) and by 0.8% with metformin/placebo (from 7.5% to 6.7%), resulting in a treatment difference of -0.3% at study end (P = .0035). In addition, metformin/colesevelam significantly reduced LDL-C (-16.3%), total cholesterol (-6.1%), non-high-density lipoprotein cholesterol (-8.3%), apolipoprotein B (-8.0%), and high-sensitivity C-reactive protein (-17%) and increased apolipoprotein A-I (+4.4%) and triglycerides (+18.6%) versus metformin/placebo (P<.01 for all). The proportions of patients who achieved recommended goals with metformin/colesevelam versus metformin/placebo, respectively, were as follows: A1C <7.0% (67% versus 56% [P = .0092]), LDL-C <100 mg/dL (48% versus 18% [P<.0001]), and composite A1C <7.0% + LDL-C <100 mg/dL (40% versus 12% [P<.0001]). Safety and tolerability were similar between the treatment groups.
  
  
  CONCLUSIONS
  Metformin plus colesevelam may be a valid option for initial therapy to achieve glycemic and lipid goals safely in early type 2 diabetes.
authors.affiliation: Dallas Diabetes and Endocrine Center at Medical City, Dallas, Texas, USA. juliorosenstock@dallasdiabetes.com
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.forename: Vivian A
authors.initials: VA
authors.lastname: Fonseca
authors.forename: W Timothy
authors.initials: WT
authors.lastname: Garvey
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Goldberg
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Handelsman
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Abby
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Lai
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Jin
authors.forename: Soamnauth
authors.initials: S
authors.lastname: Misir
authors.forename: Sukumar
authors.initials: S
authors.lastname: Nagendran
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jones
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000499:Allylamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis*; 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; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D013997:Time Factors; D055815:Young Adult
chemical_list: D000499:Allylamine; D000924:Anticholesteremic Agents; D001786:Blood Glucose; D008078:Cholesterol, LDL; D000069472:Colesevelam Hydrochloride; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008055:Lipids; D008687:Metformin; C517652:hemoglobin A1c protein, human