Alcohol consumption is a leading and preventable risk factor contributing to the global burden of disease, accounting for nearly 10 % of all deaths among individuals aged 15–49 years and approximately 139 million disability-adjusted life years (DALYs) (Díaz et al., 2025, Meza et al., 2022). The health risks associated with alcohol use are closely related to both the duration and quantity of consumption, leading to increased mortality from road traffic injuries, suicide, violence, cardiovascular, neurologic, pancreatic and liver disease, as well as different types of cancer (Meza et al., 2022). Although most individuals who consume alcohol do not develop alcohol use disorder (AUD), an estimated 111.2 million people worldwide are affected (Danpanichkul et al., 2025). Importantly, recent evidence indicates that there is no safe level of alcohol consumption (Arab et al., 2025), challenging previous assumptions that low to moderate use may be harmless or even beneficial, and positioning excessive alcohol intake as a major public health concern.

A multidisciplinary approach that integrates prevention, early diagnosis, treatment, and long-term management of complications is essential in the care of patients with AUD, with the primary goals of achieving sustained abstinence and preventing relapse. Psychosocial interventions are a cornerstone of a holistic treatment strategy and are most effective when integrated with pharmacotherapy. Currently, the strongest evidence supports the use of acamprosate and oral naltrexone for treating AUD (McPheeters et al., 2023). However, these established treatments have notable limitations that can restrict their clinical use; for instance, naltrexone requires caution in patients with impaired liver function (Mar et al., 2023) and is contraindicated for those using opioids or with opioid dependence, while acamprosate is contraindicated in patients with moderate to severe renal impairment (Mar et al., 2023). Additionally, disulfiram is strongly discouraged in patients with cirrhosis due to the risk of severe hepatotoxicity, and baclofen should be prescribed with caution in individuals with a history of hepatic encephalopathy, given its sedative effects and potential to induce drowsiness (Menge et al., 2025). Moreover, despite ongoing efforts, the global prevalence of AUD increased by 14.66 % between 2000 and 2021 (Danpanichkul et al., 2025) and approximately 40 % of patients will relapse within the first three years of treatment. These restrictions on the current available pharmacotherapies, coupled with high relapse rates and increased prevalence, underscore the urgent need for novel and more effective therapeutic options for AUD.

Preclinical studies in mice (Brunchmann et al., 2019) and nonhuman primates (Thomsen et al., 2019) have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may reduce alcohol intake and attenuate relapse-like drinking behavior. GLP-1 is an incretin hormone secreted by intestinal L-cells that stimulates insulin secretion from pancreatic beta-cells, inhibits glucagon release, and delays gastric emptying (Müller et al., 2019, Zheng et al., 2024). GLP-1RAs are approved by the European Medicines Agency and the U.S. Food and Drug Administration (FDA) for the treatment of type 2 diabetes and obesity (Alfaris et al., 2024), and the dual agonist for the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors tirzepatide is also FDA approved for obstructive sleep apnea in adults with obesity (Anderer, 2025). Since alcohol and other substances of misuse are mediated by the same neural reward pathways as food (Volkow et al., 2013), GLP-1RAs can potentially modulate brain regions involved in reward and addiction. GLP-1 receptors are expressed in key dopaminergic regions such as the ventral tegmental area (VTA) and nucleus accumbens (NAc), where their activation influences dopamine signaling (Brunchmann et al., 2019, Volkow et al., 2013). Experimental data suggest that GLP-1RAs can reduce alcohol-induced dopamine release in the NAc (Chuong et al., 2023), supporting their potential to modulate central mechanisms associated with substance use. Given that the clinical efficacy of GLP-1RAs in this context remains uncertain and no prior meta-analysis has comprehensively addressed these emerging findings, we conducted a systematic review and meta-analysis to evaluate the association between GLP-1RA use and alcohol intake, heavy drinking, progression to cirrhosis, alcohol-related events, liver-related outcomes, adverse events, and mortality compared to non-use.