The benefits of GLP-1 drugs beyond obesity

Glucagon-like peptide–1–based medicines have weight loss–independent actions Glucagon-like peptide–1 (GLP-1) is secreted from gut endocrine cells in response to food ingestion and acts as an incretin hormone to potentiate glucose-dependent insulin secretion. Pharmacological GLP-1 receptor (GLP- 1R) activation reduced glucagon secretion (which raises blood glucose) and gastric emptying, leading to the development of GLP-1 therapies for the treatment of type 2 diabetes (T2D). GLP-1R is expressed on several pancreatic islet cell types and within multiple regions of the central nervous system. Subsequent studies revealed that exogenous GLP-1 administration inhibited food intake through brain GLP-1R activation in animals and humans, leading to weight loss. The decades-long use of GLP-1 medicines, principally acylated peptides such as liraglutide and semaglutide, for the treatment of obesity and T2D ( 1 ) has revealed that they also exert pleiotropic actions beyond glucose and weight control, such as reduction of heart and kidney diseases. There are several potential mechanisms underlying these benefits, such as reducing systemic inflammation ( 2 ), which have implications for future clinical applications and drug development.