文摘
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 ?.5 to ?.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--76) or placebo (n--81) 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: ?43?nmol/L, p--.0001) versus placebo; reductions were also seen in large, small, and very small LDL particle concentrations (all p--.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: ??nmol/L, p--.82) that resulted from a lowering in small VLDL particle concentration (baseline: 45?nmol/L; LS mean treatment difference: ??nmol/L, p--.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--.20), due to increases in the large (baseline: 5?μmol/L; LS mean treatment difference: +0.5?μmol/L, p--.007) and medium (baseline: 3?μmol/L; LS mean treatment difference: +0.8?μmol/L, p--.02) HDL subclasses. Conclusions Colesevelam monotherapy in subjects with T2DM resulted in generally favorable changes in certain lipoprotein subclass profiles compared with placebo.