PMID- 22836068
OWN - NLM
STAT- MEDLINE
DCOM- 20121130
LR  - 20221207
IS  - 1933-2874 (Print)
IS  - 1876-4789 (Linking)
VI  - 6
IP  - 4
DP  - 2012 Jul-Aug
TI  - Initial combination therapy with metformin plus colesevelam improves lipoprotein 
      particles in patients with early type 2 diabetes mellitus.
PG  - 318-24
LID - 10.1016/j.jacl.2012.05.005 [doi]
AB  - 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-naive 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 mumol/L; P = .03 [4.5%; P = 
      .01]) versus metformin plus placebo. CONCLUSION: 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.
CI  - Copyright (c) 2012 National Lipid Association. Published by Elsevier Inc. All 
      rights reserved.
FAU - Goldberg, Ronald B
AU  - Goldberg RB
AD  - Division of Endocrinology, Diabetes and Metabolism, University of Miami Miller 
      School of Medicine, Miami, FL 33136, USA. rgoldber@med.miami.edu
FAU - Rosenson, Robert S
AU  - Rosenson RS
FAU - Hernandez-Triana, Eric
AU  - Hernandez-Triana E
FAU - Misir, Soamnauth
AU  - Misir S
FAU - Jones, Michael R
AU  - Jones MR
LA  - eng
SI  - ClinicalTrials.gov/NCT00570739
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120529
PL  - United States
TA  - J Clin Lipidol
JT  - Journal of clinical lipidology
JID - 101300157
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Apolipoprotein A-I)
RN  - 0 (Apolipoproteins B)
RN  - 0 (Cholesterol, HDL)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Triglycerides)
RN  - 48G762T011 (Allylamine)
RN  - 9100L32L2N (Metformin)
RN  - P4SG24WI5Q (Colesevelam Hydrochloride)
SB  - IM
MH  - Adult
MH  - Allylamine/*analogs & derivatives/therapeutic use
MH  - Anticholesteremic Agents/*therapeutic use
MH  - Apolipoprotein A-I/blood
MH  - Apolipoproteins B/blood
MH  - Cholesterol, HDL/blood
MH  - Cholesterol, LDL/blood
MH  - Colesevelam Hydrochloride
MH  - Diabetes Mellitus, Type 2/*diagnosis
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Drug Therapy, Combination
MH  - Female
MH  - Glycated Hemoglobin/analysis
MH  - Humans
MH  - Hyperlipidemias/*drug therapy
MH  - Lipoproteins, LDL/blood
MH  - Male
MH  - Metformin/*therapeutic use
MH  - Middle Aged
MH  - Placebo Effect
MH  - Triglycerides/blood
EDAT- 2012/07/28 06:00
MHDA- 2012/12/10 06:00
CRDT- 2012/07/28 06:00
PHST- 2012/03/27 00:00 [received]
PHST- 2012/05/17 00:00 [revised]
PHST- 2012/05/23 00:00 [accepted]
PHST- 2012/07/28 06:00 [entrez]
PHST- 2012/07/28 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - S1933-2874(12)00222-X [pii]
AID - 10.1016/j.jacl.2012.05.005 [doi]
PST - ppublish
SO  - J Clin Lipidol. 2012 Jul-Aug;6(4):318-24. doi: 10.1016/j.jacl.2012.05.005. Epub 
      2012 May 29.