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

Purpose: 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.