103-OR: The Glucagon-Like Peptide-1 Analog, Liraglutide Is a Safe and Effective Treatment of Bile Acid Malabsorption: A Proof of Concept Study

Abstract

Bile acid malabsorption (BAM) is caused by excessive spill-over of bile acids to the colon and is estimated to affect ∼1% of the general population. It is a socially debilitating disease with watery diarrhea and high stool frequency as main symptoms. BAM is diagnosed by the 75selenium homotaurocholic acid test (SeHCAT) measuring the retention of bile acids. Bile acid sequestrant (BAS) treatment, which is the only recommended treatment of BAM, is associated with poor effect and low compliance. Case reports suggest that the glucagon-like peptide 1 receptor analog (GLP-1RA) liraglutide may be an effective treatment of BAM. In this double-blind, double-dummy, non-inferiority study, nondiabetic individuals with SeHCAT-verified BAM, age 18-75 years and BMI 18.5-40 kg/m2 were randomized to receive the GLP-1RA liraglutide (uptitrated to 1.8 mg per day) or the BAS colesevelam (1.875 mg × 2 per day) for 6 weeks prior to a 7-day run-in period without treatment. SeHCAT was made at baseline, week 3 and week 6. The primary outcome was the proportion of patients experiencing a reduction in stool frequency of ≥25% per day. Of 52 randomized subjects (18 males, 34 females, mean age 50.2 years and BMI 29.9 kg/m2), one patient from each group dropped out due to gastrointestinal side effects. At end-of-treatment, 20 (77%) individuals on liraglutide had experienced a reduction in stool frequency of ≥25% per day vs. 13 (50%) on colesevelam treatment, corresponding to a statistically superior risk difference of -0.27 (one-sided 95% CI: -1; -0.06). In contrast to the colesevelam-treated group, the liraglutide-treated group exhibited a significant increase in SeHCAT values resulting in significantly higher values at end-of-treatment (mean (SD) 8.9 (7.3) vs. 0.9 (2.0) %, P<0.0001). In conclusion, we show that liraglutide enhances the reabsorption of bile acids and constitutes a safe and effective treatment of BAM which is superior compared to current standard of care (colesevelam). Disclosure M. L. Kårhus: None. A. Brønden: None. J. Forman: None. A. Haaber: None. E. Langholz: None. T. Vilsbøll: Consultant; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Gilead Sciences, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk, Sanofi, Sun Pharmaceutical Industries Ltd. D. P. Sonne: None. F. K. Knop: Advisory Panel; Self; MSD Corporation, Novo Nordisk A/S, Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Pharmacosmos, Zealand Pharma A/S, Research Support; Self; Novo Nordisk A/S, Zealand Pharma A/S, Speaker’s Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S. Funding Novo Nordisk Foundation (NNF17OC0029710); A.P. Møller and Chastine Mc-Kinney Møller Foundation (19-L-0002)