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


OBJECTIVE
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.
Preventive Cardiology, The University of Chicago Medicine, Chicago, IL 60637; Radiant Development, Radiant Research Inc, 515 N. State Street, Suite 2700, Chicago, IL 60654.
Michael H
MH
Davidson
Michael
M
Rooney
Elisabeth
E
Pollock
Joan
J
Drucker
Young
Y
Choy
D000499:Allylamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood*; D000069472:Colesevelam Hydrochloride; D050171:Dyslipidemias / Q000097:blood* / Q000188:drug therapy*; D005215:Fasting / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000009:adverse effects* / Q000627:therapeutic use; D012449:Safety
D001786:Blood Glucose; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D009525:Niacin; D000499:Allylamine; D000069472:Colesevelam Hydrochloride
Colesevelam; Dyslipidemia; Fructosamine; Hemoglobin A(1c); Impaired fasting glucose; LDL cholesterol; Niacin