Liraglutide Superior to Colesevelam in Treating Bile Acid Diarrhea

Liraglutide outperformed colesevelam in reducing stool frequency for patients with bile acid diarrhea, in research based in Denmark.

A team, led by Martin L Kårhus, Center for Clinical Metabolic Research, Copenhagen University Hospital Herlev and Gentofte, investigated the safety and efficacy of liraglutide for the treatment of bile acid diarrhea.

The Disease

Bile acid diarrhea is generally underdiagnosed, but still affects about 1-2% of the general population. There are case reports showing liraglutide, a glucagon-like peptide 1 receptor agonist, could be an option to treat this patient population.

In the randomized, double-blind, active-comparator, double-dummy, non-inferiority clinical trial, the investigators examined 52 patients aged 18-75 years at the Center for Clinical Metabolic Research at Copenhagen University Hospital–Herlev and Gentofte in Hellerup, Denmark between April 1, 2019 and January 31, 2021. Each participant had ⁷⁵selenium-homotaurocholic acid test (SeHCAT)-verified moderate-to-severe primary bile acid diarrhea.

The patients were randomized to receive a once daily subcutaneous injection uptrirated from 0.6-1.8 mg dose of liraglutide for 3 weeks or 3 capsules of 625 mg twice daily colesevelam for 6 weeks following 1 run-in week with no treatment.

The investigators sought primary endpoints of the proportion of patients experiencing a reduction in daily stool frequency of 25% or greater after 6 weeks.

The team also set a non-inferiority limit of 15% in favor of colesevelam.

Superiority for Liraglutide

The results show 77% (n = 20) of participants on liraglutide and 50% (n = 13) of patients treated with colesevelam experienced a 25% or greater reduction in stool frequency. This equated to a significant risk difference of -27% in favor of liraglutide (one-sided 95% CI, -100 to -6).

There were some adverse events identified, but they were all mild nausea for a duration of 10-21 days. This was reported by 6 participants in the liraglutide group and 1 participant in the colesevelam group.

“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,” the authors wrote.

Other Uses for Liraglutide

Liraglutide has shown efficacy treating other conditions in the past, including type 1 diabetes, obesity, and cardiovascular diseases.

Last year, a randomized clinical trial investigated the effect of liraglutide on body fat distribution in a high-risk population.

Patients aged ≥35 years with BMI ≥30 kg/m2 or ≥27 kg/m2 with metabolic syndrome were assigned liraglutide (3.0mg.ml) or placebo.

After a median 36-week treatment, data show liraglutide had a reduction in visceral/ectopic fat. Investigators noted proportionally greater effects in the abdominal viscera at 2 times greater and 6 times greater in the liver, compared with overall body weight.

The investigators saw liraglutide reduced visceral adipose tissue by a placebo-corrected tissue of about 11%, as well as a significant reduction in liver fat by 33% and reductions in inflammation and fasting glucose.

The study, “Safety and efficacy of liraglutide versus colesevelam for the treatment of bile acid diarrhea: a randomized, double-blind, active-comparator, non-inferiority clinical trial,” was published online in The Lancet Gastroenterology & Hepatology.