Glucagon-Like Peptide-1 Receptor Agonists for Bile Acid Diarrhea: Emerging Evidence and Clinical Implications

胰高血糖素样肽-1受体激动剂治疗胆汁酸腹泻:新证据和临床意义

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Abstract

Bile acid diarrhea (BAD) is an underrecognized cause of chronic diarrhea that makes a significant contribution to the symptom burden and impaired quality of life. Despite increasing awareness, BAD is frequently misdiagnosed as diarrhoea-predominant irritable bowel syndrome (IBS-D), leading to delayed diagnosis and incomplete symptom control. Current management relies primarily on bile acid sequestrants, which are effective for many patients but limited by poor tolerability, variable adherence, and incomplete response in a subset, prompting interest in alternative therapeutic approaches targeting bile acid dysregulation. Advances in understanding enterohepatic signaling have highlighted the role of the farnesoid X receptor-fibroblast growth factor 19 (FXR-FGF19) axis in regulating bile acid synthesis, secretion, and motility. In parallel, glucagon-like peptide-1 (GLP-1) receptor agonists, which are commonly used in the treatment of metabolic diseases, affect gastrointestinal motility, secretion, and neurohormonal signaling by mechanisms that overlap with those that are implicated in BAD. Emerging clinical studies, including randomized trials comparing GLP-1-based therapy with established bile acid sequestrants, have begun to explore their potential role in BAD, although the current evidence base remains limited and investigational. This narrative review synthesizes peer-reviewed evidence examining the biological rationale, diagnostic context, and clinical data relevant to GLP-1 receptor agonists in BAD. Literature was identified primarily by PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE) searches supplemented by manual screening of reference lists of key reviews and clinical studies and integrated narratively because of heterogeneity of study design, exposure definitions, and outcome measures. Current evidence suggests that GLP-1 receptor agonists represent a biologically plausible area of investigation for selected patients with persistent symptoms despite standard therapy. This review does not advocate routine clinical use but aims to contextualize emerging BAD-specific and mechanistic data to inform hypothesis generation, patient selection, and future research. Available data are still limited, and GLP-1 receptor agonists have not been established as a treatment for BAD. Further prospective studies with standardized outcomes are needed to clarify their role and inform evidence-based clinical practice.

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