Therapeutic Potential of Incretin-Based Therapies for Alcohol Use Disorder: A Narrative Review of Available Clinical...

Alcohol use disorder (AUD) remains a major global health burden, but pharmacological treatment options are limited, and there is an urgent need for novel molecular targets for the treatment of AUD. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been used for more than 2 decades to treat type 2 diabetes and subsequently overweight and obesity. Unexpected effects, including reduced alcohol intake, have been reported by patients as well as by clinicians, and these (often anecdotal) reports have been supported by a growing body of data from large registry studies; target trial emulation analyses; preclinical experiments with mice, rats, and nonhuman primates; and randomized clinical trials associating the use of GLP-1RAs with reduced alcohol consumption. This convergence has sparked growing interest in GLP-1RAs as a novel therapeutic strategy for AUD. In this narrative review, we synthesize current evidence on the effects of GLP-1RAs in individuals with AUD. To date, only 3 randomized controlled trials have examined GLP-1RAs in AUD, showing reductions in alcohol cue brain reactivity and alcohol consumption, particularly among individuals with overweight or obesity. We also report on observational data, including large registry studies, target trial emulation analyses, and real-world data, which have consistently associated GLP-1RA use with reduced alcohol consumption. Case reports and social media analyses further corroborate reductions in alcohol craving and consumption. Mechanistically, emerging evidence points to modulation of reward circuitry, incentive salience, gastric emptying, and metabolic signaling. Overall, GLP-1RAs represent a promising and mechanistically novel approach to AUD treatment, warranting confirmation in larger, long-term randomized trials.