Antiinflammatory actions of glucagon-like peptide-1–based therapies beyond metabolic benefits
Chi Kin Wong, Daniel J. Drucker
Chi Kin Wong, Daniel J. Drucker
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Review Series

Antiinflammatory actions of glucagon-like peptide-1–based therapies beyond metabolic benefits

Abstract

Therapies based on glucagon-like peptide-1 (GLP-1) reduce rates of cardiovascular and chronic kidney disease in people with type 2 diabetes and/or obesity, with ongoing clinical trials investigating their effects in people with metabolic liver disease, arthritis, and both substance use and neurodegenerative disorders. Acute and chronic activation of GLP-1 receptor signaling also reduces systemic and tissue inflammation in mice and humans, through weight loss–dependent and –independent mechanisms, actions that may contribute to the expanding spectrum of clinical benefits ascribed to GLP-1 medicines. In this Review, we highlight current understanding of the direct and indirect antiinflammatory effects and mechanisms of GLP-1 medicines in both preclinical and clinical studies, covering emerging concepts, clinical relevance, and areas of uncertainty that require further investigation.

Authors

Chi Kin Wong, Daniel J. Drucker

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Figure 4

Potential cellular targets mediating the antiinflammatory effects of GLP-1 medicines.

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Potential cellular targets mediating the antiinflammatory effects of GLP...
GLP-1Rs are expressed at low levels in most peripheral organs and often in rare cell types. In osteoarthritis, a well-established inflammatory condition, GLP-1 medicines likely exert their effects through multiple pathways. These may include direct actions on joint tissues such as the synovium and cartilage. Interactions between GLP-1 medicines, the intestinal immune system including IELs, and the gut microbiota may also influence joint inflammation. Additionally, the central nervous system represents another site of GLP-1 action, contributing to the regulation of systemic inflammation through indirect mechanisms. Other common inflammatory diseases and metabolic complications may respond to GLP-1 medicines in a similar manner.