TY - JOUR
T1 - Initial combination therapy with metformin plus colesevelam improves lipoprotein particles in patients with early type 2 diabetes mellitus
AU - Goldberg, Ronald B.
AU - Rosenson, Robert S.
AU - Hernandez-Triana, Eric
AU - Misir, Soamnauth
AU - Jones, Michael R.
N1 - Funding Information:
Dr. Goldberg has received research grants from Abbott Laboratories, GlaxoSmithKline, and Roche .
Funding Information:
Dr. Hernandez-Triana has served on scientific advisory boards for Eli Lilly and Company, Novo Nordisk, Pfizer Inc, and Roche, and received consulting fees and research grants from Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, MSD, Novartis, and sanofi-aventis . Dr. Hernandez-Triana and his immediate family do not have ownership interest and or stocks of any pharmaceutical or device company.
Funding Information:
Dr. Rosenson has participated in advisory boards for Abbott Laboratories, Amgen Inc., AstraZeneca, Hoffman-La Roche Inc., LipoScience Inc., and sanofi-aventis, and owns stock in LipoScience, Inc. Dr. Rosenson's institution has received research grants from Amgen Inc. and Hoffman-La Roche Inc.
Funding Information:
This study was funded by Daiichi Sankyo, Inc . Medical writing services and editorial assistance provided by Karen Stauffer, PhD, Lucy Whitehouse, and Sushma Soni of in Science Communications were funded by Daiichi Sankyo, Inc.
PY - 2012/7
Y1 - 2012/7
N2 - 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.
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-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.
KW - Apolipoprotein
KW - Bile acid sequestrant
KW - Colesevelam
KW - Lipoprotein particles
KW - Low-density lipoprotein
KW - Type 2 diabetes mellitus
UR - http://www.scopus.com/inward/record.url?scp=84864216037&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864216037&partnerID=8YFLogxK
U2 - 10.1016/j.jacl.2012.05.005
DO - 10.1016/j.jacl.2012.05.005
M3 - Article
C2 - 22836068
AN - SCOPUS:84864216037
VL - 6
SP - 318
EP - 324
JO - Journal of Clinical Lipidology
JF - Journal of Clinical Lipidology
SN - 1933-2874
IS - 4
ER -
