Effect of colesevelam and niacin on low-density lipoprotein cholesterol and glycemic control in subjects with dyslipidemia and impaired fasting glucose

Abstract

Background: Niacin monotherapy in patients with dyslipidemia and impaired fasting glucose (IFG) may result in hyperglycemia. Colesevelam has the unique dual approvals to lower low-density lipoprotein cholesterol (LDL-C) and to improve glycemic control in type 2 diabetes mellitus.

Objectives: The aim of our study was to evaluate the effect of combined colesevelam and niacin treatment on LDL-C-lowering and glycemic control in subjects with IFG and dyslipidemia.

Methods: Men or women ≥ 18 years of age, with dyslipidemia (non-high-density lipoprotein cholesterol ≥ 100 mg/dL and ≤ 220 mg/dL; high-density lipoprotein cholesterol < 60 mg/dL) and fasting plasma glucose (FPG) ≥ 90 mg/dL and ≤ 145 mg/dL were randomly assigned 1:1 to colesevelam (3750 mg/d) with niacin titration (n = 70) or placebo with niacin titration (n = 70) over 12 weeks. Niacin was titrated from 500 mg/d up to a maximum of 2000 mg/d as tolerated, and all subjects took enteric-coated aspirin daily. Lipid and glycemic efficacy parameters were assessed as well as safety evaluations of adverse events, vital signs, alanine aminotransferase, aspartate aminotransferase, hematology, and urinalysis.

Results: Adjunct colesevelam had significantly greater LDL-C-lowering effect than niacin alone (placebo); -20.67% vs -12.86%, respectively (P = .0088). Niacin-mediated increases in FPG were significantly less with adjunct colesevelam (1.8 mg/dL vs 6.7 mg/dL; P = .0046), and fewer colesevelam subjects had increases of ≥ 10 mg/dL in FPG (8 vs 17, respectively). Adjunct colesevelam resulted in significantly smaller increases in hemoglobin A1c than placebo (0.06% vs 0.18%, respectively; P = .005). Consistent with hemoglobin A1c and FPG changes, fructosamine levels significantly decreased with colesevelam treatment (-5.0 μmol/L) but increased with placebo (3.0 μmol/L; P =.0255).

Conclusions: Colesevelam as an adjunct to niacin therapy further lowers LDL-C while obviating the adverse effects of niacin on glucose metabolism in patients with dyslipidemia and IFG.

Keywords: Colesevelam; Dyslipidemia; Fructosamine; Hemoglobin A(1c); Impaired fasting glucose; LDL cholesterol; Niacin.