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.

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.

• Authors: Ronald B Goldberg, Robert S Rosenson, Eric Hernandez-Triana, Soamnauth Misir, Michael R Jones
• Journal: Journal of clinical lipidology (J Clin Lipidol) 2012 Jul-Aug Vol. 6 Issue 4 Pg. 318-24 ISSN: 1933-2874 [Print] United States
• PMID: 22836068 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anticholesteremic Agents
• Apolipoprotein A-I
• Apolipoproteins B
• Cholesterol, HDL
• Cholesterol, LDL
• Glycated Hemoglobin A
• Lipoproteins, LDL
• Triglycerides
• Allylamine
• Metformin
• Colesevelam Hydrochloride

Topics

• Adult
• Allylamine (analogs & derivatives, therapeutic use)
• Anticholesteremic Agents (therapeutic use)
• Apolipoprotein A-I (blood)
• Apolipoproteins B (blood)
• Cholesterol, HDL (blood)
• Cholesterol, LDL (blood)
• Colesevelam Hydrochloride
• Diabetes Mellitus, Type 2 (diagnosis)
• Double-Blind Method
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Glycated Hemoglobin (analysis)
• Humans
• Hyperlipidemias (drug therapy)
• Lipoproteins, LDL (blood)
• Male
• Metformin (therapeutic use)
• Middle Aged
• Placebo Effect
• Triglycerides (blood)