Effect of Colesevelam HCl Monotherapy on Lipid Particles in Type 2 Diabetes Mellitus

Robert S Rosenson,Michael R Jones,Hubert S Chou,Scott P Rigby

doi:10.1007/s10557-014-6516-y

Abstract

PurposeIn addition to lowering hemoglobin A1C, colesevelam has been shown to improve the atherogenic lipoprotein profile of subjects with type 2 diabetes mellitus (T2DM) when used in combination with metformin and/or sulfonylureas. A recent study evaluated the effects of colesevelam as antidiabetes monotherapy in adults with T2DM who had inadequate glycemic control (hemoglobin A1C ≥7.5 to ≤9.5 %) with diet and exercise alone; we report here the effects on lipoprotein particle subclasses.MethodsSubjects were randomized to receive oral colesevelam 3.75 g/day (n = 176) or placebo (n = 181) for 24 weeks. Changes in lipoprotein particle subclasses were determined by nuclear magnetic resonance spectroscopy.ResultsAt Week 24 with last observation carried forward, colesevelam produced a reduction in total low-density lipoprotein (LDL) particle concentration (baseline: 1,611 nmol/L; least-squares [LS] mean treatment difference: −143 nmol/L, p < 0.0001) versus placebo; reductions were also seen in large, small, and very small LDL particle concentrations (all p < 0.05). There was also a reduction in total very low-density lipoprotein (VLDL) and chylomicron particle concentration (baseline: 88 nmol/L; LS mean treatment difference: −1 nmol/L, p = 0.82) that resulted from a lowering in small VLDL particle concentration (baseline: 45 nmol/L; LS mean treatment difference: −5 nmol/L, p = 0.03). In addition, with colesevelam there was an increase in total high-density lipoprotein (HDL) particle concentration versus placebo (baseline: 31 μmol/L; LS mean treatment difference: +0.6 μmol/L, p = 0.20), due to increases in the large (baseline: 5 μmol/L; LS mean treatment difference: +0.5 μmol/L, p = 0.007) and medium (baseline: 3 μmol/L; LS mean treatment difference: +0.8 μmol/L, p = 0.02) HDL subclasses.ConclusionsColesevelam monotherapy in subjects with T2DM resulted in generally favorable changes in certain lipoprotein subclass profiles compared with placebo.

Highlights

Insulin resistance and type 2 diabetes mellitus (T2DM) are associated with a variety of lipid and lipoprotein abnormalities, including reduced high-density lipoprotein (HDL) cholesterol levels, elevated triglyceride levels, and an altered distribution of lipoprotein particles [1]
At Week 24 with last observation carried forward, colesevelam produced a reduction in total low-density lipoprotein (LDL) particle concentration versus placebo; reductions were seen in large, small, and very small LDL particle concentrations
Colesevelam monotherapy in subjects with T2DM resulted in generally favorable changes in certain lipoprotein subclass profiles compared with placebo

Summary

Introduction

Insulin resistance and type 2 diabetes mellitus (T2DM) are associated with a variety of lipid and lipoprotein abnormalities, including reduced high-density lipoprotein (HDL) cholesterol levels, elevated triglyceride levels, and an altered distribution of lipoprotein particles [1]. VLDL particle sizes are increased and LDL and HDL particle sizes are decreased in patients with insulin resistance or T2DM. These effects are seen despite normal or near-normal levels of LDL cholesterol and total cholesterol [3]. This altered distribution of lipoprotein particles ( LDL particles) is relevant to cardiovascular disease (CVD) risk [4]. Determining which agents increase HDL-P is important, as HDL-P is inversely correlated with carotid intima-media thickness and cardiovascular events, and administering an agent that increases HDL-P may help to further reduce CVD risk [10,11,12, 15]

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