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Glucose and Lipid Effects

Harold E. Bays, MD; Ronald B. Goldberg, MD; Kenneth E. Truitt, MD; Michael R. Jones, PhD

Arch Intern Med. 2008;168(18):1975-1983.

Background  Bile acid sequestrants are a well-accepted class of cholesterol-lowering drugs. Over the last decade, small studies have indicated that these agents may also lower glucose levels in patients with type 2 diabetes mellitus (T2DM).

Methods  This 26-week, randomized, double-blind, placebo-controlled, parallel-group study was conducted between August 2004 and July 2006 at 54 sites in the United States and 2 in Mexico to determine the effects of colesevelam hydrochloride, a bile acid sequestrant, in patients with inadequately controlled T2DM (hemoglobin A_1c [HbA_1c] level, 7.5%-9.5% [baseline HbA_1c level, 8.1%]), who were receiving metformin monotherapy or metformin combined with additional oral anti–diabetes mellitus drugs. In total, 316 subjects were randomized (159 to colesevelam hydrochloride, 3.75 g/d, and 157 to matching placebo). The primary efficacy parameter was mean placebo-corrected change in HbA_1c level from baseline to week 26 (analysis was on an intent-to-treat population using a last-observation-carried-forward approach).

Results  Colesevelam lowered the mean HbA_1c level compared with placebo at week 26 (–0.54%; P < .001). Similar results were observed in the metformin monotherapy (–0.47%; P = .002) and combination therapy cohorts (–0.62%; P < .001). In addition, colesevelam significantly (1) lowered fasting plasma glucose (–13.9 mg/dL P = .01), fructosamine (–23.2 µmol/L; P < .001), total cholesterol (TC) (–7.2%; P < .001), low-density lipoprotein cholesterol (LDL-C) (–15.9%; P < .001), apolipoprotein B (–7.9%; P < .001), non–high-density lipoprotein cholesterol (HDL-C) (–10.3%; P < .001), and high-sensitivity C-reactive protein (–14.4%; P = .02) levels and (2) improved other measures of glycemic response, as well as TC/HDL-C, LDL-C/HDL-C, non–HDL-C/HDL-C, and apolipoprotein B/apolipoprotein A-I ratios (P < .003 for all). Triglyceride, HDL-C, and apolipoprotein A-I levels were not statistically significantly increased.

Conclusion  Colesevelam improves glycemic and lipid parameters in patients with T2DM inadequately controlled with metformin-based therapy.

Trial Registration  clinicaltrials.gov Identifier: NCT00147719

Author Affiliations: Louisville Metabolic and Atherosclerosis Research Center Inc, Louisville, Kentucky (Dr Bays); Lipid Disorders Clinic, Division of Endocrinology, Diabetes, and Metabolism, and the Diabetes Research Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida (Dr Goldberg); Daiichi Sankyo Pharma Development, Edison, New Jersey (Dr Truitt); and Daiichi Sankyo, Inc, Parsippany, New Jersey (Dr Jones).

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