Colesevelam Enhances Odds of Clinical Remission for Bile Acid Diarrhea

There were no serious adverse events in the group of patients treated with colesevelam.

New research supports the use of colesevelam for the treatment of patients with bile acid diarrhea.1

A team, led by Christian Borup, MD, Department of Internal Medicine, Zealand University Hospital, determined the efficacy and safety of colesevelam in patients with bile acid diarrhea.

Bile Acid Diarrhea

Despite being a common cause, bile acid diarrhea is often overlooked as a cause of chronic watery diarrhea. Plasma 7α-hydroxy-4-cholesten-3-one (C4) can be an alternative to the gold standard tauroselcholic [75Se] acid (SeHCAT) test. However, there is low-certainly evidence that supports sequestrant treatment, including colesevelam.

In the randomized, double-blind, placebo-controlled, investigator-initiated phase 4 trial, the investigators enrolled 168 consecutive patients without inflammatory bowel disease (IBD) attending SeHCAT testing for suspected bile acid diarrhea at 4 secondary care centers in the Netherlands between Oct. 25, 2018 and July 1, 2021.

Each participant received either 12 days of treatment with colesevelam 625 mg (n = 84) or placebo (n = 84). The starting dose was 2 capsules twice daily, titrated to effect during the first 5 days of treatment.

The investigators also blinded C4 and SeHCAT diagnostic results during treatment. All patients with diarrhea with a daily mean of 3 or more bowel movements or 1 or more watery bowel movements were treated. The team also defined remission as the absence of both of those criteria during treatment days 6-12.


The investigators sought primary outcomes of the intention-to-treat remission rate in bile acid diarrhea diagnosed by C4 concentration greater than 46 ng/mL and secondary outcomes of the intention-to-treat remission rate in bile acid diarrhea diagnosed by SeHCAT retention of 10% or less.

The results show 41 patients had C4 concentrations greater than 46 ng/mL. Of this group, 22 were in the colesevelam group and 19 were treated with the placebo. For the primary outcome, 64% (n = 14) of the colesevelam group and 16% (n = 3) achieved remission (adjusted odds ratio [aOR]. 9.1; 95% confidence interval [CI], 1.9-62.8; P = 0.011).

After analyzing the secondary outcomes, the investigators found 75 patients had retention of less than 10%, 37 in the colesevelam cohort and 38 in the placebo group.

In the colesevelam cohort, 59% (n = 22) achieved remission, compared to 13% (n = 5) of the placebo group (aOR, 11.1; 95% CI, 3.4-45.6; P = 0.00020).

In the safety analysis, the investigators did not identify any serious adverse events and found the common adverse events were transient. However, 5 patients who achieved the primary outcome who were treated with colesevelam had abdominal pain, while 9 had bloating, and 4 had nausea.

For the placebo group, 4 had abdominal pain, 4 had bloating, and 1 had nausea. There were no withdraws because of adverse events.

“Colesevelam was superior to placebo at inducing remission of bile acid diarrhea diagnosed with C4 concentration greater than 46 ng/mL,” the authors wrote. “Secondary outcome data suggest similar efficacy treating SeHCAT-defined bile acid diarrhea. Colesevelam was safe during the treatment.”


Borup, C., Vinter-Jensen, L., Jørgensen, S. P., Wildt, S., Graff, J., Gregersen, T., Zaremba, A., Borup Andersen, T., Nøjgaard, C., Timm, H. B., Rainteau, D., Hansen, S. H., Rumessen, J. J., & Munck, L. K. (2023). Efficacy and safety of Colesevelam for the treatment of bile acid diarrhoea: A double-blind, randomised, placebo-controlled, phase 4 clinical trial. The Lancet Gastroenterology & Hepatology.