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GLP-1 receptor agonists: exploration of transformation from metabolic regulation to multi-organ therapy

Bing Gong1,2,3, Couwen Li1,2, Zhuang'e Shi1,2

  • 1Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China.

Frontiers in Pharmacology
|September 29, 2025
PubMed

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) show broad therapeutic potential beyond diabetes and obesity. Their anti-inflammatory and organ-protective effects are being explored for various diseases.

Area of Science:

  • Pharmacology
  • Endocrinology
  • Immunology

Background:

  • Glucagon-like peptide-1 receptor agonists (GLP-1RAs) were initially developed for type 2 diabetes and obesity.
  • GLP-1RAs exhibit pleiotropic effects beyond glycemic control, influencing immune and inflammatory pathways, autophagy, and endoplasmic reticulum stress.

Purpose of the Study:

  • To review the mechanistic expansion of GLP-1RAs from metabolic regulators to systemic modulators.
  • To explore the therapeutic repurposing of GLP-1RAs across various organ systems and diseases.

Main Methods:

  • Literature review of preclinical and clinical studies.
  • Synthesis of evidence on GLP-1 signaling mechanisms.
  • Analysis of therapeutic applications in diverse disease models.

Main Results:

  • GLP-1 signaling modulates inflammation, autophagy, pyroptosis, and endoplasmic reticulum stress.
  • Clinical trials confirm cardiovascular and renal protection, leading to expanded approvals.
  • Investigational data suggest benefits in liver disease, respiratory disorders, neurodegenerative conditions, and more.

Conclusions:

  • GLP-1RAs demonstrate significant potential for therapeutic repurposing due to their multi-organ effects.
  • Further research is warranted to validate their efficacy in a wide range of non-metabolic diseases.
Keywords:
GLP-1 receptor agonistgut microbiotamolecular mechanismsmulti-organ protectiontherapeutic repurposing

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