Abstract 11700: The Effect of Colesevelam and Niacin on Low-density Lipoprotein Cholesterol and Plasma Glucose

Abstract

Background: Patients with impaired fasting glucose (IFG) often have dyslipidemia that is treated with niacin. Frequently, niacin elevates plasma glucose. Colesevelam has both lipid and glucose lowering properties and may have a dual benefit as an adjunct treatment to niacin in subjects with IFG and dyslipidemia.

Objectives: To assess colesevelam effectiveness on lowering of low-density-lipoprotein cholesterol (LDL-C) and glycemic control in subjects with IFG taking niacin for dyslipidemia.

Methods: Men or women ≥18 years of age, with dyslipidemia (non-HDL-C ≥100 mg/dL and ≤220 mg/dL); HDL-C <60 mg/dL; and fasting plasma glucose (FPG) ≥90 mg/dL and ≤145 mg/dL were randomized 1:1 to colesevelam (3750 mg/day) with niacin titration (n=70) or placebo with niacin titration (n=70) over 12 weeks. Niacin was titrated from 500 mg/day up to a maximum of 2000 mg/day 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, ALT/AST, hematology and urinalysis.

Results: Subjects on colesevelam as adjunct to niacin therapy had significantly greater LDL-C lowering compared to niacin alone (placebo); -20.67% vs -12.86%, respectively (p=0.0088). Niacin-mediated increases in FPG were significantly less with colesevelam than with placebo (1.8 mg/dL vs 6.7 mg/dL; p = 0.0046), and fewer subjects on colesevelam than on placebo had increases of ≥10 mg/dL in FPG. Colesevelam treated subjects also had significantly smaller increases in HbA1c than placebo (0.06% vs 0.18%, respectively; p = 0.005). Consistent with HbA1c and FPG changes, fructosamine levels significantly decreased with colesevelam treatment (-4.0 µmol/L) but increased with placebo (3.0 µmol/L; p = 0.0255).

Conclusions: The present study demonstrated that adjunct colesevelam to niacin therapy effectively lowered LDL-C in patients with IFG, and furthermore significantly improved glycemic indices (FPG, HbA1c, and fructosamine) compared to niacin alone (placebo). In conclusion, colesevelam as adjunct to niacin therapy further lowers LDL-C while obviating the adverse effects of niacin on glucose metabolism in patients with dyslipidemia and impaired fasting glucose.