Colesevelam hydrochloride therapy in patients with type 2 diabetes mellitus treated with metformin: glucose and lipid effects.

Article Details

Citation

Bays HE, Goldberg RB, Truitt KE, Jones MR

Colesevelam hydrochloride therapy in patients with type 2 diabetes mellitus treated with metformin: glucose and lipid effects.

Arch Intern Med. 2008 Oct 13;168(18):1975-83. doi: 10.1001/archinte.168.18.1975.

PubMed ID
18852398 [ View in PubMed
]
Abstract

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 micromol/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.

DrugBank Data that Cites this Article

Pharmaco-metabolomics
DrugDrug GroupsMetaboliteChangeDescription
ColesevelamApprovedFructosamine
decreased
Colesevelam decreases the level of Fructosamine in the blood
ColesevelamApprovedHDL cholesterol
increased
Colesevelam increases the level of HDL cholesterol in the blood
ColesevelamApprovedGlucose
decreased
Colesevelam decreases the level of Glucose in the blood
ColesevelamApprovedTotal cholesterol
decreased
Colesevelam decreases the level of Total cholesterol in the blood
ColesevelamApprovedLDL cholesterol
decreased
Colesevelam decreases the level of LDL cholesterol in the blood
MetforminApprovedGlucose
decreased
Metformin decreases the level of Glucose in the blood