Effect of colesevelam HCl monotherapy on lipid particles in type 2 diabetes mellitus.
OBJECTIVE
In 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.


METHODS
Subjects 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.


RESULTS
At 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.


CONCLUSIONS
Colesevelam monotherapy in subjects with T2DM resulted in generally favorable changes in certain lipoprotein subclass profiles compared with placebo.
Cardiometabolic Disorders, Mt. Sinai Heart, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, MC1 Level, New York, NY, 10029, USA, robert.rosenson@mssm.edu.
Robert S
RS
Rosenson
Scott P
SP
Rigby
Michael R
MR
Jones
Hubert S
HS
Chou
D000328:Adult; D000499:Allylamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002914:Chylomicrons / Q000097:blood; D000069472:Colesevelam Hydrochloride; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D016018:Least-Squares Analysis; D008074:Lipoproteins / Q000097:blood*; D008297:Male
D000499:Allylamine; D000924:Anticholesteremic Agents; D002914:Chylomicrons; D000069472:Colesevelam Hydrochloride; D006442:Glycated Hemoglobin; D008074:Lipoproteins; C517652:hemoglobin A1c protein, human