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.
| Original language | English |
|---|---|
| Pages (from-to) | 318-324 |
| Number of pages | 7 |
| Journal | Journal of Clinical Lipidology |
| Volume | 6 |
| Issue number | 4 |
| DOIs | |
| State | Published - Jul 1 2012 |
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Keywords
- Apolipoprotein
- Bile acid sequestrant
- Colesevelam
- Lipoprotein particles
- Low-density lipoprotein
- Type 2 diabetes mellitus
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Endocrinology, Diabetes and Metabolism
- Internal Medicine
- Nutrition and Dietetics
Cite this
Initial combination therapy with metformin plus colesevelam improves lipoprotein particles in patients with early type 2 diabetes mellitus. / Goldberg, Ronald B; Rosenson, Robert S.; Hernandez-Triana, Eric; Misir, Soamnauth; Jones, Michael R.
In: Journal of Clinical Lipidology, Vol. 6, No. 4, 01.07.2012, p. 318-324.Research output: Contribution to journal › Article
}
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.
PY - 2012/7/1
Y1 - 2012/7/1
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
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U2 - 10.1016/j.jacl.2012.05.005
DO - 10.1016/j.jacl.2012.05.005
M3 - Article
VL - 6
SP - 318
EP - 324
JO - Journal of Clinical Lipidology
JF - Journal of Clinical Lipidology
SN - 1933-2874
IS - 4
ER -