Gastrointestinal Adverse Effects of Elobixibat in Chronic Constipation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Citra Safitri Wirman; Rudi Erwin Kurniawan; Darmawi; Benni Iskandar

doi:10.35451/3rncke15

Authors

Citra Safitri Wirman Program Studi Magister Ilmu Biomedis, Fakultas Kedokteran, Universitas Riau
Rudi Erwin Kurniawan Departeman Ilmu Penyakit Dalam FK Inkes Medistra Lubuk Pakam
Darmawi Darmawi Departemen Histologi, Fakultas Kedokteran, Universitas Riau
Benni Iskandar Departemen Teknologi Farmasi, Sekolah Tinggi Ilmu Farmasi Riau, Indonesia

DOI:

https://doi.org/10.35451/3rncke15

Keywords:

Adverse effects, Chronic constipation, Elobixibat

Abstract

Chronic constipation is a common gastrointestinal disorder that negatively affects quality of life and increases healthcare burden worldwide. Elobixibat, an ileal bile acid transporter inhibitor, has been introduced as a novel therapy to enhance intestinal fluid secretion and improve colonic motility in patients with chronic constipation. However, concerns remain regarding gastrointestinal adverse effects, particularly their potential relationship with dosage. Therefore, this study aimed to evaluate gastrointestinal adverse effects associated with elobixibat and to assess whether these events demonstrate a dose-dependent pattern. This systematic review and meta-analysis followed the PRISMA 2020 guidelines and was registered in PROSPERO (CRD420251155537). A literature search was conducted in PubMed and ScienceDirect to identify randomized controlled trials investigating elobixibat in chronic constipation patients published up to December 2025. Study eligibility was determined using the PICOS framework. Data on adverse effects, dosage, and treatment duration were extracted and analyzed using proportional meta-analysis with a random-effects model in R Studio, and risk of bias was assessed using the RoB2 tool. Five randomized controlled trials involving 922 participants are included in the analysis. The pooled proportion of diarrhea is 21%, abdominal distension is 26%, and abdominal pain is 16%, while unspecified gastrointestinal disorders represent the most frequently reported adverse events at 49%. Overall, gastrointestinal adverse events show a dose-dependent pattern, with higher doses associated with increased event rates. These findings indicate that elobixibat is associated with dose-dependent gastrointestinal adverse effects, highlighting the importance of individualized dosing and gradual titration to improve treatment tolerability.

Downloads

Download data is not yet available.

References

[1] Nag A, Martin SA, Mladsi D, Olayinka-Amao O, Purser M, Vekaria RM. The Humanistic and Economic Burden of Chronic Idiopathic Constipation in the USA: A Systematic Literature Review. Clin Exp Gastroenterol 2020;13:255. https://doi.org/10.2147/CEG.S239205.

[2] Ota T, Kuratani S, Masaki H, Ishizaki S, Seki H, Takebe T. Impact of chronic constipation symptoms on work productivity and daily activity: A large-scale internet survey. JGH Open 2024;8. https://doi.org/10.1002/JGH3.70042.

[3] Nakajima A, Unno A, Ota T, Shoji A, Uenishi T, Igarashi A. Socioeconomic value of treatments for chronic idiopathic constipation in Japan. BMC Gastroenterology 2025 25:1 2025;25:748-. https://doi.org/10.1186/S12876-025-04334-8.

[4] Ihara E, Manabe N, Ohkubo H, Ogasawara N, Ogino H, Kakimoto K, et al. Evidence-Based Clinical Guidelines for Chronic Constipation 2023. Digestion 2025;106:62–89. https://doi.org/10.1159/000540912.

[5] Salari N, Ghasemianrad M, Ammari-Allahyari M, Rasoulpoor S, Shohaimi S, Mohammadi M. Global prevalence of constipation in older adults: a systematic review and meta-analysis. Wien Klin Wochenschr 2023;135:389–98. https://doi.org/10.1007/S00508-023-02156-W.

[6] Luo J, To WLW, Xu Q, Zhang J, Ma Y, Chow S, et al. Clinical practice guidelines for the diagnosis of constipation-predominant irritable bowel syndrome and functional constipation in adults: a scoping review. BMC Gastroenterol 2025;25. https://doi.org/10.1186/S12876-025-03774-6.

[7] Włodarczyk J, Waśniewska A, Fichna J, Dziki A, Dziki Ł, Włodarczyk M. Current Overview on Clinical Management of Chronic Constipation. J Clin Med 2021;10. https://doi.org/10.3390/JCM10081738.

[8] Chedid V, Vijayvargiya P, Camilleri M. Drug Profile Elobixibat for the Treatment of Constipation. Expert Rev Gastroenterol Hepatol 2018;12:951. https://doi.org/10.1080/17474124.2018.1522248.

[9] Nakajima A, Umeyama M, Higashikawa M, Shimada Y, Arai Y. A multicenter, postmarketing surveillance of elobixibat in patients with chronic constipation in Japan: A final analysis report. SAGE Open Med 2025;13. https://doi.org/10.1177/20503121251321659.

[10] Nakajima A, Seki M, Taniguchi S, Ohta A, Gillberg PG, Mattsson JP, et al. Safety and efficacy of elobixibat for chronic constipation: results from a randomised, double-blind, placebo-controlled, phase 3 trial and an open-label, single-arm, phase 3 trial. Lancet Gastroenterol Hepatol 2018;3:537–47. https://doi.org/10.1016/S2468-1253(18)30123-7.

[11] Nakajima A, Fujimaki M, Arai Y, Emori K. Safety and Efficacy of Elobixibat, an Ileal Bile Acid Transporter Inhibitor, in Elderly Patients With Chronic Idiopathic Constipation According to Administration Time: Interim Analysis of Post-marketing Surveillance. J Neurogastroenterol Motil 2022;28:431–41. https://doi.org/10.5056/JNM20263.

[12] Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372. https://doi.org/10.1136/BMJ.N71.

[13] Kumagai Y, Amano H, Sasaki Y, Nakagawa C, Maeda M, Oikawa I, et al. Effect of single and multiple doses of elobixibat, an ileal bile acid transporter inhibitor, on chronic constipation: A randomized controlled trial. Br J Clin Pharmacol 2018;84:2393–404. https://doi.org/10.1111/BCP.13698.

[14] Hatano T, Oyama G, Shimo Y, Ogaki K, Nishikawa N, Nakamura R, et al. Efficacy and Safety of Elobixibat in Parkinson’s Disease with Chronic Constipation: CONST-PD Study. Mov Disord Clin Pract 2024;11:352–62. https://doi.org/10.1002/MDC3.13972.

[15] Agarwal P, Jha BK, Somagoni J, B SS, Modh V, Chakilam SK, et al. Efficacy and safety of elobixibat in patients with chronic constipation-A randomized, multicenter, double-blind, placebo-controlled, parallel-group study from India. Indian J Gastroenterol 2025;44:336–44. https://doi.org/10.1007/S12664-024-01719-7.

[16] Nakajima A, Seki M, Taniguchi S. Determining an optimal clinical dose of elobixibat, a novel inhibitor of the ileal bile acid transporter, in Japanese patients with chronic constipation: a phase II, multicenter, double-blind, placebo-controlled randomized clinical trial. J Gastroenterol 2018;53:525–34. https://doi.org/10.1007/S00535-017-1383-5.

[17] Abe T, Kunimoto M, Hachiro Y, Ohara K, Inagaki M, Murakami M. Efficacy and Safety of Elobixibat in Elderly Patients with Chronic Constipation: A Single-center, Observational Study. J Anus Rectum Colon 2020;4:122. https://doi.org/10.23922/JARC.2020-006.

[18] Manabe N, Umeyama M, Ishizaki S, Ota T, Kuratani S, Katsumata R, et al. Elobixibat improves rectal sensation in patients with chronic constipation aged ≥60 years: a randomised placebo-controlled study. BMJ Open Gastroenterol 2023;10. https://doi.org/10.1136/BMJGAST-2023-001257.

[19] Sakai Y, Tsuyuguchi T, Kumagai J, Ohyama H, Kaiho T, Ohtsuka M, et al. Efficacy of elobixibat for elderly patients with chronic constipation in a clinic. World J Gastrointest Pharmacol Ther 2025;16. https://doi.org/10.4292/WJGPT.V16.I2.105801.

[20] Miner PB. Elobixibat, the first-in-class Ileal Bile Acid Transporter inhibitor, for the treatment of Chronic Idiopathic Constipation. Expert Opin Pharmacother 2018;19:1381–8. https://doi.org/10.1080/14656566.2018.1508450.

[21] Nakajima A, Taniguchi S, Kurosu S, Gillberg PG, Mattsson JP, Camilleri M. Efficacy, long‐term safety, and impact on quality of life of elobixibat in more severe constipation: Post hoc analyses of two phase 3 trials in Japan. Neurogastroenterology and Motility 2019;31:e13571. https://doi.org/10.1111/NMO.13571.

[22] Al-Dury S, Marschall HU. Ileal Bile Acid Transporter Inhibition for the Treatment of Chronic Constipation, Cholestatic Pruritus, and NASH. Front Pharmacol 2018;9. https://doi.org/10.3389/FPHAR.2018.00931.

[23] Yang D, Lyu C, He K, Pang K, Guo Z, Wu D. Bile Acid Diarrhea: From Molecular Mechanisms to Clinical Diagnosis and Treatment in the Era of Precision Medicine. Int J Mol Sci 2024;25. https://doi.org/10.3390/IJMS25031544.

[24] Odaka T, Tominaga K. Uncontrolled, Open-Label Pre-Dinner Administration of Elobixibat in Japanese Adults with Chronic Constipation: A Retrospective Chart Review. Curr Ther Res Clin Exp 2020;93. https://doi.org/10.1016/j.curtheres.2020.100616.