二甲双胍联合考来维仑治疗早期 2 型糖尿病患者可改善脂蛋白颗粒。

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

机构信息

Division of Endocrinology, Diabetes and Metabolism, University of Miami Miller School of Medicine, Miami, FL 33136, USA.

出版信息

J Clin Lipidol. 2012 Jul-Aug;6(4):318-24. doi: 10.1016/j.jacl.2012.05.005. Epub 2012 May 29.

DOI:10.1016/j.jacl.2012.05.005

PMID:22836068

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.

摘要

背景

胆酸螯合剂考来维仑已被证明可显著降低原发性高脂血症或 2 型糖尿病（T2DM）成人的低密度脂蛋白颗粒浓度（LDL-P）。

目的

评估二甲双胍联合考来维仑初始联合治疗对 T2DM 患者脂蛋白颗粒的影响（次要疗效变量）。

方法

这是一项为期 16 周、随机、双盲、安慰剂对照的研究，纳入了未经药物治疗的 T2DM 成年患者，糖化血红蛋白 6.5%-10.0%，低密度脂蛋白胆固醇（LDL-C）≥100mg/dL，且三酰甘油<500mg/dL。患者按 1:1 随机分为二甲双胍（滴定至 1700mg/天）联合考来维仑 3.75g/天的开放标签组或二甲双胍联合安慰剂的双盲组。

结果

共 286 名患者被随机分组（二甲双胍联合考来维仑组[n=145]；二甲双胍联合安慰剂组[n=141]）。与二甲双胍联合安慰剂相比，二甲双胍联合考来维仑治疗可显著降低 LDL-C（平均治疗差异：-16.3%）、总胆固醇（-6.1%）、非高密度脂蛋白胆固醇（-8.3%）和载脂蛋白 B（-8.0%），并显著增加三酰甘油（中位数治疗差异：18.6%）和载脂蛋白 A-I（平均治疗差异：4.4%；均 P<.001）。二甲双胍联合考来维仑可显著降低总 LDL-P（平均治疗差异：绝对值变化-186nmol/L[百分比变化-11.7%]；均 P<.0001），主要归因于小 LDL-P 的减少，同时增加了总极低密度脂蛋白颗粒浓度（平均治疗差异：绝对值变化 6nmol/L；P=.03[百分比变化 8.3%；P=.06]）和总高密度脂蛋白颗粒浓度（1.0μmol/L；P=.03[4.5%；P=.01]），与二甲双胍联合安慰剂相比。