Ítem
Acceso Abierto
Initial combination therapy with metformin plus colesevelam improves lipoprotein particles in patients with early type 2 diabetes mellitus
Título de la revista
Autores
Goldberg, Ronald B.
Rosenson, Robert S.
Hernandez-Triana, Eric
Misir, Soamnauth
Jones, Michael R.
Resumen
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 less than 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 less than .001). Metformin plus colesevelam significantly reduced total LDL-P (mean treatment difference: absolute change -186 nmol/L [percent change -11.7%]; both P less than .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 ?mol/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. © 2012 National Lipid Association. All rights reserved.
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Keywords
Apolipoprotein B , Combination , Colesevelam , Hemoglobin a1c , High density lipoprotein cholesterol , Lipoprotein , Low density lipoprotein cholesterol , Metformin , Placebo , Triacylglycerol , Very low density lipoprotein , Adult , Article , Cholesterol blood level , Controlled study , Correlational study , Double blind procedure , Drug dose increase , Drug dose titration , Drug efficacy , Evening dosage , Female , Hemoglobin blood level , Human , Lipoprotein blood level , Major clinical study , Male , Morning dosage , Multicenter study , Non insulin dependent diabetes mellitus , Open study , Priority journal , Randomized controlled trial , Treatment duration , Triacylglycerol blood level , Adult , Allylamine , Anticholesteremic Agents , Apolipoprotein A-I , Apolipoproteins B , Cholesterol , Cholesterol , Diabetes Mellitus , Double-Blind Method , Drug Administration Schedule , Drug Therapy , Female , Hemoglobin A , Humans , Hyperlipidemias , Lipoproteins , Male , Metformin , Middle Aged , Placebo Effect , Triglycerides , Apolipoprotein , Bile acid sequestrant , Colesevelam , Lipoprotein particles , Low-density lipoprotein , Type 2 diabetes mellitus
