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 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.

• 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
• License: Abierto (Texto Completo)