The Anti-Fibrotic Potential of GLP-1 and GIP Receptor Agonists in Chronic Inflammatory Disorders: Mechanisms and Therapeutic Horizons

Abstract

Fibrosis, characterised by the excessive deposition of extracellular matrix via activated fibroblasts, is a pathological feature of several chronic inflammatory disorders, which collectively contribute significantly to global morbidity and mortality. Despite this, current anti-fibrotic therapies are of limited efficacy. However, incretin-based therapies, primarily glucagon-like peptide-1 (GLP-1) receptor agonists, are now emerging as candidate drugs for modulating fibrotic signalling pathways. This review synthesises the growing body of preclinical and clinical evidence that incretin receptor agonists exert direct and indirect anti-fibrotic effects. We detail the molecular mechanisms and survey the promising data across hepatic, cardiac, renal, lung, and joint tissues, which underscore the potential for repurposing of this drug class as a therapeutic strategy for fibro-inflammatory conditions.

Keywords

Fibrosis / Incretins / GLP-1 / GIP / TGF-β / Myofibroblasts / Synovial fibroblasts / Osteoarthritis / Semaglutide / Liraglutide / Dulaglutide / MASLD / Kidney disease

Acknowledgements

The study of the literature was carried out at the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC).

Ethics Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Funding

S.W.J. has received funding from the Medical Research Council [MR/W026961/1] and Arthritis UK (21530, 21812), which contributed to the original research articles summarised in this review.

Declaration of Competing Interest

The author declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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