Abstract 13046: Colesevelam in Combination with Metformin Significantly Reduces Low-Density Lipoprotein Particle Concentration in Patients with Early Type 2 Diabetes
Elevated low-density lipoprotein (LDL) cholesterol (LDL-C) is a risk factor for cardiovascular (CV) events in patients (pts) with type 2 diabetes mellitus (T2DM). However, residual CV risk remains high even in pts with well-controlled LDL-C. Studies suggest that LDL particle (LDL-P) concentration may explain this risk. A 16-week, randomized, double-blind, placebo (PBO)-controlled, multicenter study was conducted to evaluate the glucose- and lipid-lowering effect of initial combination therapy with metformin (MET) + colesevelam (COL) in pts with early T2DM. In total, 286 antidiabetes-drug-naive adults with T2DM (A1C 6.5%−10.0%), LDL-C ≥100 mg/dL, and triglycerides (TG) <500 mg/dL were randomized 1:1 to open-label MET (initiated at 850 mg/d; uptitrated to 1700 mg/d) + double-blind COL 3.75 g/d (n=145) or PBO (n=141). Lipoprotein particle concentrations and sizes were determined by nuclear magnetic resonance spectroscopy. At baseline, 11 pts (8% [MET+COL]) and 9 pts (6% [MET+PBO]) were on statin therapy. In pts receiving MET+COL, LDL-C and apoB levels decreased by 16.3% (baseline [MET+COL/MET+PBO, respectively]: 130/135 mg/dL) and 8.0% (109/112 mg/dL), while TG and apoA-I levels increased by 18.6% (176/181 mg/dL) and 5.6% (132/132 mg/dL) (all P<0.002 vs MET+PBO). LDL-P concentration was significantly reduced with MET+COL (P<0.001 vs MET+PBO) with no significant change in LDL-P size between the groups. There were small but significant increases in very-low-density lipoprotein particle concentration and size with MET+COL (P<0.05 vs MET+PBO for both). High-density lipoprotein particle (HDL-P) concentration and size significantly increased with MET+COL (P<0.05 and P<0.01, respectively, vs MET+PBO). Early treatment with MET+COL compared with MET+PBO improved the overall atherogenic lipoprotein profile by significantly reducing LDL-C levels and LDL-P concentration and by significantly increasing HDL-P concentration in pts with T2DM.
- © 2010 by American Heart Association, Inc.