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Review
. 2025 Apr;36(4):301-315.
doi: 10.1016/j.tem.2025.01.002. Epub 2025 Feb 10.

Glucagon-like peptide-1 receptor agonism and end-organ protection

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Free article
Review

Glucagon-like peptide-1 receptor agonism and end-organ protection

Samuel Daniels et al. Trends Endocrinol Metab. 2025 Apr.
Free article

Abstract

Identification of exendin-4 (a glucagon-like peptide-1 receptor agonist, GLP-1RA) in Gila monster venom may be regarded as one of the most serendipitous discoveries of recent times. GLP-1RAs are now an established therapeutic approach in type 2 diabetes (T2D), body weight management, and cardiovascular (CV) risk protection. Furthermore, there is a growing platform of evidence that GLP-1RA has extended benefit in renal, hepatic, respiratory, and neurological diseases. One can speculate on the biological advantage of exendin-4 to the Gila monster, but for humankind GLP-1RAs are peptides with significant potential to improve disease-related outcomes. We report on the latest evidence and mechanisms for GLP-1RA-mediated end-organ protection that uniquely highlight its future development potential across multiple disease areas.

Keywords: cardiovascular; end-organ protection; glucagon-like peptide-1 (GLP-1); kidney; liver; neurodegenerative; respiratory.

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Conflict of interest statement

Declaration of interests S.D., C.K., and V.E.R.P. are employees of and stockholders in AstraZeneca; P.S. has received institutional research funding from AstraZeneca. V.E.R.P. holds patent WO2021140174A1 (Glucagon and GLP-1R co-agonists for the treatment of chronic kidney disease and diabetic kidney disease in type 2 diabetes).

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