GLP-1 receptor agonists in alcohol use disorder and alcohol-associated liver disease
Ashwani K Singal, Lorenzo Leggio
GLP-1 is a hormone produced by intestinal L-type enteroendocrine cells, endocrine pancreas, and nucleus tractus solitarius neurons in the brain. GLP-1 acts via the GLP-1 receptor and provides beneficial effects on food intake, energy homoeostasis, glucose metabolism, hepatic function, and inflammation. A growing body of literature suggests a role of GLP-1 in alcohol-associated liver disease (ALD) and addiction, including alcohol use disorder (AUD), which poses the question of whether GLP-1 receptor agonists might have a dual beneficial effect in ALD and AUD (appendix). Addiction is a chronic relapsing but treatable brain disease with high morbidity and mortality. Specific to alcohol addiction, people with AUD often present with psychiatric or medical comorbidities, or both, including ALD. Alcohol is a leading cause of liver disease and is now the main cause of cirrhosis and the leading indication for liver transplantation.1 Few medications are approved for AUD; therefore, developing new medications for AUD is crucial.2 The GLP-1 signalling pathway is emerging as a gut–brain neuroendocrine system with important mechanistic roles related to addiction, including AUD. In the past decade, a growing body of preclinical evidence shows that GLP-1 receptor agonists lead to a reduction in alcohol drinking, selfadministration, preference, and other alcohol-related outcomes (eg, conditioned place preference, a proxy for alcohol reward) in mouse, rat, and non-human primate models of excessive alcohol use
