Initial combination therapy with metformin plus colesevelam improves lipoprotein particles in patients with early type 2 diabetes mellitus

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...

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Autores:
Tipo de recurso:
Fecha de publicación:
2012
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/22299
Acceso en línea:
https://doi.org/10.1016/j.jacl.2012.05.005
https://repository.urosario.edu.co/handle/10336/22299
Palabra clave:
Apolipoprotein B
Chylomicron
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
Double-Blind Method
Drug Administration Schedule
Female
Humans
Hyperlipidemias
Male
Metformin
Middle Aged
Placebo Effect
Triglycerides
Apolipoprotein
Bile acid sequestrant
Colesevelam
Lipoprotein particles
Low-density lipoprotein
Type 2 diabetes mellitus
Combination
Type 2
LDL
LDL
HDL
Glycosylated
Cholesterol
Cholesterol
Diabetes Mellitus
Drug Therapy
Hemoglobin A
Lipoproteins
Rights
License
Abierto (Texto Completo)
Description
Summary: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.