Colesevelam hydrochloride (cholestagel): a new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects

Arch Intern Med. 1999 Sep 13;159(16):1893-900. doi: 10.1001/archinte.159.16.1893.


Objectives: To compare colesevelam hydrochloride (Cholestagel), a nonabsorbed hydrogel with bile acid-sequestering properties, with placebo for its lipid-lowering efficacy, its effects on laboratory and clinical safety parameters, and the incidence of adverse events.

Methods: Following diet and placebo lead-in periods, placebo or colesevelam was administered at 4 dosages (1.5, 2.25, 3.0, or 3.75 g/d) for 6 weeks with morning and evening meals to men and women with hypercholesterolemia (low-density lipoprotein cholesterol level >4.14 mmol/L [>160 mg/dL]). Patients returned to the clinic every 2 weeks throughout the treatment period for lipid parameter measurements and adverse event assessments. Samples were collected for serum chemistry profiles, hematologic studies, coagulation studies, and vitamin level assessment at baseline and after 6 weeks of treatment.

Results: Among the 149 patients randomized, 137 completed the study. Low-density lipoprotein cholesterol concentrations decreased in a dosage-dependent manner by 0.11 mmol/L (4.2 mg/dL) (1.8%) in the 1.5-g/d colesevelam treatment group and up to 1.01 mmol/L (39 mg/dL) (19.1%) in the 3.75-g/d colesevelam treatment group. Low-density lipoprotein cholesterol concentrations at the end of treatment were significantly reduced from baseline levels in the 3.0- and 3.75-g/d colesevelam treatment groups (P = .01 and P<.001, respectively). Total cholesterol levels demonstrated a similar response to colesevelam treatment, with an 8. 1% decrease from baseline in the 3.75-g/d treatment group (P<.001). High-density lipoprotein cholesterol levels rose significantly in the 3.0- and 3.75-g/d colesevelam treatment groups, by 11.2% (P=.006) and 8.1% (P=.02), respectively. Median triglyceride levels did not change from baseline, nor were there any significant differences between treatment groups. The incidence of adverse events was similar among all groups.

Conclusions: Colesevelam therapy is effective for lowering low-density lipoprotein cholesterol concentrations in persons with moderate hypercholesterolemia. It lacks the constipating effect of other bile acid sequestrants, demonstrating the potential for increased compliance.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Allylamine / adverse effects
  • Allylamine / analogs & derivatives*
  • Allylamine / chemistry
  • Allylamine / therapeutic use
  • Bile Acids and Salts / metabolism*
  • Cholagogues and Choleretics / adverse effects
  • Cholagogues and Choleretics / chemistry
  • Cholagogues and Choleretics / therapeutic use*
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Colesevelam Hydrochloride
  • Digestive System / drug effects*
  • Double-Blind Method
  • Female
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / metabolism*
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / drug therapy*
  • Hypertriglyceridemia / metabolism*
  • Lipids / blood*
  • Male
  • Middle Aged
  • Triglycerides / blood


  • Bile Acids and Salts
  • Cholagogues and Choleretics
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Lipids
  • Triglycerides
  • Allylamine
  • Colesevelam Hydrochloride