Colon to Rectum
Lancet Gastroenterol Hepatol. 2022;7(10):922–31
Safety and efficacy of liraglutide versus colesevelam for the treatment of bile acid diarrhea: A randomized, double-blind, active-comparator, non-inferiority clinical trial
Background: Bile acid diarrhea is an underdiagnosed disease estimated to affect 1–2% of the general population. Case reports indicate that the glucagon-like peptide 1 receptor agonist liraglutide might be an effective treatment for bile acid diarrhea. The aim of this study was to investigate the safety and efficacy of liraglutide for the treatment of bile acid diarrhea.
Methods: The authors conducted a randomized, double-blind, active-comparator, double-dummy, non-inferiority clinical trial at the Center for Clinical Metabolic Research at Copenhagen University Hospital, Herlev and Gentofte, Hellerup, Denmark. Patients aged 18–75 years with 75selenium-homotaurocholic acid test (SeHCAT)-verified moderate-to-severe primary bile acid diarrhea were randomly assigned (1:1) to receive liraglutide (1 daily subcutaneous injection uptitrated from 0.6–1.8 mg per day over 3 weeks) or colesevelam (3 capsules of 625 mg twice daily), the standard of care, for 6 weeks following 1 run-in week with no treatment. The primary end point was the proportion of participants experiencing a reduction in daily stool frequency of 25% or greater after 6 weeks. Data from all participants were included in the analysis of the primary outcome. The non-inferiority limit was set to 15% in favor of colesevelam.
Findings: Between April 1, 2019, and January 31, 2021, 52 patients were enrolled; 26 were assigned to liraglutide and 26 to colesevelam. 20 of 26 participants (77%) on liraglutide and 13 of 26 (50%) on colesevelam experienced a 25% or greater reduction in stool frequency, corresponding to a significant risk difference of -27% in favor of liraglutide (1-sided 95% confidence interval: -100 to -6). Liraglutide was therefore superior to colesevelam in reducing daily stool frequency. Mild nausea with a duration of 10–21 days was reported by 6 participants in the liraglutide group and by 1 participant in the colesevelam group. No other adverse events were reported.
Interpretation: The superiority of liraglutide compared with colesevelam in reducing stool frequency suggests consideration of liraglutide as a potential new treatment modality for bile acid diarrhea, although larger confirmatory trials powered for superiority are warranted.