Concomitant Reduction in Low-Density Lipoprotein Cholesterol and Glycated Hemoglobin With Colesevelam Hydrochloride in Patients With Type 2 Diabetes: A Pooled Analysis

Abstract

Colesevelam hydrochloride (COL), a bile acid sequestrant indicated as an adjunct to diet and exercise for reducing low-density lipoprotein cholesterol (LDL-C) in patients with primary hypercholesterolemia, was shown in a pilot study to reduce both glycated hemoglobin (HbA1c) and LDL-C in patients with type 2 diabetes mellitus (T2DM). Three double-blind, placebo-controlled trials in T2DM have now independently confirmed the HbA1c and LDL-C reductions with COL. In each of the primary studies, a significant mean treatment difference in HbA1c (-0.54%, -0.50%, and -0.54%) and LDL-C (-15.9%, -12.8%, and -16.7%) resulted from the addition of 3.75 grams/day of COL to existing metformin, insulin, or sulfonylurea-based therapy, respectively, in patients with T2DM inadequately controlled on their current antidiabetic regimen. Here we report the results of a pooled analysis of data for the 1018 patients included in the three primary studies. By study end, HbA1c, fasting plasma glucose (FPG), LDL-C, total cholesterol (TC), non-high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (ApoB), and high-sensitivity C-reactive protein (hsCRP) were significantly reduced with COL versus placebo. Triglyceride (TG) and ApoA-I were significantly increased in the COL group relative to placebo. HDL-C did not change in either group, and the between-group treatment difference was small and not significant. Results of this pooled analysis are consistent with results reported previously in each of the primary COL studies and indicate that the HbA1c and LDL-C-lowering effects of COL are consistent, occurring regardless of whether COL is added to metformin, insulin, or sulfonylurea-based therapy. In conclusion, COL represents a novel therapeutic option by significantly lowering both LDL-C and HbA1c in patients with T2DM, two important treatment goals to forestall vascular complications.