Colesevelam hydrochloride to treat hypercholesterolemia and improve glycemia in prediabetes: a randomized, prospective study.
OBJECTIVE
To assess the effect of the bile acid sequestrant colesevelam hydrochloride in patients with hypercholesterolemia and prediabetes.


METHODS
In this 16-week, randomized, double-blind study, adults with untreated prediabetes (2-hour postoral glucose tolerance test [OGTT] glucose > or =140 to 199 mg/dL, fasting plasma glucose [FPG] > or =110 to 125 mg/dL, or both), low-density lipoprotein cholesterol (LDL-C) > or =100 mg/dL, and triglycerides <500 mg/dL were randomly assigned to receive colesevelam (3.75 g/d) or placebo. The primary end point was percent change in LDL-C from baseline to week 16 with last observation carried forward. Secondary end points included change in FPG, hemoglobin A1c (A1C), and 2-hour post-OGTT glucose level from baseline to week 16 and attainment of LDL-C and FPG targets.


RESULTS
In total, 216 patients were randomized (colesevelam, 108; placebo, 108). In comparison with placebo, colesevelam significantly reduced LDL-C (mean treatment difference, -15.6%), non-high-density lipoprotein cholesterol (-9.1%), total cholesterol (-7.2%), apolipoprotein B (-8.1%) (P<.001 for all the foregoing), FPG (median, -2.0 mg/dL; P = .02), and A1C (mean, -0.10%; P = .02). Colesevelam did not significantly change 2-hour post-OGTT glucose (-1.9 mg/dL; P = .75) or high-density lipoprotein cholesterol (-0.5%; P = .80). In addition, colesevelam significantly increased triglyceride levels relative to placebo (median, 14.3%; P<.001). The proportion of patients achieving target levels with colesevelam versus placebo, respectively, was as follows: LDL-C <100 mg/dL (29% versus 11%; P<.001), A1C <6.0% (37% versus 25%; P = .05), FPG <110 mg/dL (48% versus 56%; P = .97), and normalization of glucose (FPG <100 mg/dL [40% versus 23%; P = .06]). Colesevelam had a weight-neutral effect and was well tolerated.


CONCLUSIONS
Colesevelam is an option for managing the lipid profile and normalizing glucose levels in patients with hypercholesterolemia and prediabetes. Further study is warranted to determine whether colesevelam slows or prevents progression of prediabetes to type 2 diabetes.
Handelsman
Yehuda
Y
Metabolic Institute of America, Tarzana, California 91356, USA. yhandelsman@yahoo.com
Goldberg
Ronald B
RB
Garvey
W Timothy
WT
Fonseca
Vivian A
VA
Rosenstock
Julio
J
Jones
Michael R
MR
Lai
Yu-Ling
YL
Jin
Xiaoping
X
Misir
Soamnauth
S
Nagendran
Sukumar
S
Abby
Stacey L
SL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000499:Allylamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis*; D001835:Body Weight / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood; D000069472:Colesevelam Hydrochloride; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000097:blood / Q000150:complications*; D013223:Statistics as Topic; D055815:Young Adult
D000499:Allylamine; D000924:Anticholesteremic Agents; D001786:Blood Glucose; D008078:Cholesterol, LDL; D000069472:Colesevelam Hydrochloride; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human