GLP-1 RAs Lower Risk of Liver Damage and Death in Alcohol Use, reveals research
Researchers have determined in a new study that the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) lower the risk of alcohol-related liver disease, mortality, and risky alcohol use in patients with heavy drinking behaviors. These results are based on an observational target trial emulation of electronic health records of U.S. veterans. The study indicates that the GLP-1 RAs, medications with their primary indication for type 2 diabetes and obesity, potentially provide protective benefits against alcohol-induced liver outcomes and decrease alcohol consumption. The study was published in the American Journal of Gastroenterology by Binu V John and colleagues.
GLP-1 receptor agonists have attracted interest for their glucose-lowering and weight-reducing action as well as through anecdotal evidence of reduced alcohol cravings among users. As excessive alcohol consumption is a major cause of liver disease and death, researchers aimed to ascertain whether GLP-1 RAs might offer quantifiable clinical benefits in such a population. The research replicated a target trial with data based on actual cases of veterans with alcohol use disorder history, defined as a positive Alcohol Use Disorders Identification Test–Concise (AUDIT-C) screen.
The study evaluated data through January 3, 2017, to September 30, 2024, with follow-up continuing through death, occurrence of liver-related outcomes, or end of the study. Each treatment-initiating participant was matched with a comparable patient who did not take GLP-1 RAs to provide equivalent comparisons.
The high-volume study employed electronic health records of the U.S. Veterans Affairs to simulate a target trial. It comprised 8040 new GLP-1 RA users with a positive AUDIT-C score, each 1:1 matched with 8040 non-users with a positive alcohol screen. The main outcome was a composite of four serious conditions: hepatic decompensation, hepatocellular carcinoma (HCC), liver-related death, and all-cause mortality. The secondary outcome assessed the odds of persistent harmful alcohol use, again measured in terms of follow-up AUDIT-C scores. Semaglutide, which is also widely prescribed GLP-1 RA, was also examined by dose to see if higher dosing provided greater protection against bad outcomes.
Key Findings
• Users of GLP-1 RA had a 30% reduced chance of having liver-related events and/or dying (adjusted hazard ratio [aHR] 0.70, 95% CI 0.56–0.87).
• All-cause mortality was lowered by 57% among users of GLP-1 RA (aHR 0.43, 95% CI 0.37–0.49).
Among Semaglutide users, every 1 mg/week increase in dose was linked with:
• A 50% reduced risk of liver-related outcomes (aHR 0.50, 95% CI 0.29–0.88)
• A 67% reduced risk of mortality (aHR 0.33, 95% CI 0.19–0.58)
• The use of GLP-1 RA was linked to 25% lower odds of positive testing for harmful alcohol use during follow-up (adjusted odds ratio [aOR] 0.75, 95% CI 0.68–0.82)
This real-world evidence target trial emulation demonstrated that GLP-1 RA therapy substantially decreased the risk of complications related to the liver, all-cause death, and dangerous use of alcohol in U.S. veterans with alcohol misuse. The results provide encouraging evidence of the potential for GLP-1 RA repurposing for more general use in liver disease prevention and substance use disorder treatment, supporting future clinical investigation and consideration in practice.
Reference:
John BV, Bastaich D, Marchetti D, Perumalswami P, Mustafa MZ, Dahman B; Veterans Analysis of Liver Disease (VALID) group of investigators. Association of GLP-1 Receptor Agonists with Liver-Related Outcomes and All-Cause Mortality in Patients with Harmful Alcohol Use: A Target Trial Emulation Study. Am J Gastroenterol. 2025 Jun 10. doi: 10.14309/ajg.0000000000003585. Epub ahead of print. PMID: 40488647.
