Liraglutide Noninferior to Colesevelam in Patients With Bile Acid Diarrhea

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Researchers compared the safety and efficacy of liraglutide with colesevelam for treating bile acid diarrhea.

Liraglutide compared with colesevelam was superior for reducing stool frequency among patients with bile acid diarrhea, according to a study published in The Lancet Gastroenterology & Hepatology.

For the randomized, double-blind, double-dummy, noninferiority study, researchers screened 65 patients and included 52 with selenium-homotaurocholic acid test-verified moderate to severe primary bile acid diarrhea. Patients were randomly assigned 1:1 to receive liraglutide (subcutaneous injection uptitrated from 0.6 to 1.8 mg for 3 weeks once daily) or colesevelam (3 capsules of 625 mg for 6 weeks twice daily, followed by 1 week without treatment).

The primary endpoint was the proportion of patients who achieved at least a 25% reduction in daily stool frequency after 6 weeks. Secondary endpoints included the proportion of patients with remission of bile acid diarrhea symptoms and changes in QOL as assessed by a questionnaire.

In the liraglutide group, 77% of patients attained at least a 25% reduction in daily stool frequency compared with 50% of patients in the colesevelam group. Results of the study suggested that liraglutide was superior to colesevelam in relation to the primary endpoint; however, the study was not powered to show superiority. Patients who received liraglutide also had a higher rate of symptom remission (65%) compared with patients who received colesevelam (42%), though the difference was not statistically significant. There were no significant differences between the groups in QOL assessments.

Limitations of the study include having only White participants, the relatively short treatment window, and not being powered to show superiority. Larger, superiority-powered trials are warranted, as is a cost benefit analysis on the use of liraglutide over colesevelam, the study authors explained.

“The GLP-1RA liraglutide, a well known and safe drug used for the treatment of type 2 diabetes and obesity, was observed in this study to be superior to colesevelam (considered the standard of care in bile acid diarrhoea) in reducing stool frequency by 25% or greater in patients with moderate-to-severe bile acid diarrhea over 6 weeks, suggesting consideration of liraglutide as a potential treatment modality for patients with bile acid diarrhoea, although further studies are warranted in this setting,” the study authors wrote.

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Pleases see the original reference for a full list of the author’s disclosures.

Reference

Kårhus ML, Brønden A, Forman JL, et al. Safety and efficacy of liraglutide versus colesevelam for the treatment of bile acid diarrhoea: a randomized, double-blind, active-comparator, non-inferiority clinical trial. Lancet Gastroenterol Hepatol. Published online July 19, 2022. doi:10.1016/S2468-1253(22)00198-4