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 A1c [HbA1c] level, 7.5%-9.5% [baseline HbA1c 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 HbA1c 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 HbA1c 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-HDLC/ 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.
ASJC Scopus subject areas
- Internal Medicine