Colesevelam improved lipoprotein particle subclasses in patients with prediabetes and primary hyperlipidaemia

Abstract

Background: A randomised, double-blind, placebo-controlled study evaluated lipid-and glucose-lowering effects of colesevelam in patients with prediabetes and primary hyperlipidaemia. We report the effect of colesevelam on lipoprotein particle concentration and particle size (determined by nuclear magnetic resonance spectroscopy) in these patients. Methods: Adults with prediabetes (World Health Organization criteria), low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥2.6 mmol/L) and triglycerides < 500 mg/dL (<5.6 mmol/L) were randomised to colesevelam 3.75 g/day or placebo for 16 weeks. The intent-to-treat population comprised 103 colesevelam and 106 placebo recipients. Results: At the end of the study, mean reduction from baseline in total LDL particle concentration was significantly greater with colesevelam versus placebo (mean treatment difference: −113 nmol/L; p = 0.02). Increases in total very low-density lipoprotein particle concentration (VLDL-P) and high-density lipoprotein particle concentration (HDL-P) did not differ significantly between the groups; however, with colesevelam versus placebo, there were significantly (p < 0.05) greater increases in large and medium VLDL-P and large HDL-P and reductions in small VLDL-P. Mean size increases were significantly greater with colesevelam for VLDL (mean treatment difference: 5.3 nm; p < 0.0001) and HDL (0.1 nm; p = 0.002). Conclusions: Colesevelam improved the overall atherogenic lipoprotein profile in adults with prediabetes and primary hyperlipidaemia, despite potentially less favourable changes in VLDL particles.

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

“…These results are in line with previous studies showing that colesevelam decreases LDL-P and increases LDL particle size in subjects with hypercholesterolemia [31], prediabetes [32], or T2DM [20, 21]. In the previous studies in subjects with T2DM [20, 21], as in the current study, the reduction in LDL-P was largely attributable to reductions in the smaller LDL particle subclasses: small LDL-P, as well as very small LDL-P (assessed in the current study).…”

Modulation of Bile Acid Metabolism to Improve Plasma Lipid and Lipoprotein Profiles

“…At the end of the 16-week study, total cholesterol, LDL-C and apoB were significantly reduced by 7.2%, 15.6% and 8.1%, respectively, with colesevelam versus placebo. However, the treatment arm also presented with a significant increase in triglycerides (+14.3%) [ 64 ]. In 2013, the use of colesevelam (3.75 g/day) in 176 T2D patients for 24 weeks was shown to reduce total cholesterol, LDL-C and apoB by −5.1%, −11.2% and −6.5%, respectively, compared to 181 patients treated with placebo [ 65 ].…”

Hypertension and Dyslipidemia in Patients with Pre-Diabetes

“…An interesting finding in many small studies is that in addition to its LDL-C-lowering effects, colesevelam may also favorably affect carbohydrate metabolism in both diabetic and prediabetic subjects [84,85]. Despite their efficiency in reducing the levels of LDL-C as well as the incidence of CVD in patients with hypercholesterolemia, cholestyramine, and colestipol are used rarely because of their important gastrointestinal side effects.…”