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


CONCLUSIONS
Colesevelam improves glycemic and lipid parameters in patients with T2DM inadequately controlled with metformin-based therapy.
Bays
Harold E
HE
Louisville Metabolic and Atherosclerosis Research Center Inc, 3288 Illinois Ave, Louisville, KY 40213, USA. hbaysmd@aol.com
Goldberg
Ronald B
RB
Truitt
Kenneth E
KE
Jones
Michael R
MR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000499:Allylamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D000069472:Colesevelam Hydrochloride; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008055:Lipids / Q000097:blood*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
D000499:Allylamine; D000924:Anticholesteremic Agents; D001786:Blood Glucose; D000069472:Colesevelam Hydrochloride; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008055:Lipids; D008687:Metformin