GLP-1 RAs Reduce Alcohol-Related Liver Disease Risk in Patients with AUD

GLP-1 RAs are associated with a reduced risk of alcohol-related liver disease (ArLD) incidence and progression in patients with alcohol use disorder (AUD) and type 2 diabetes, according to findings from a recent study.1

Leveraging data from the TriNetX Research Network, investigators conducted a pair of retrospective cohort studies and found that compared with dipeptidyl peptidase-4 inhibitors (DPP-4is), GLP-1RA use is associated with significant clinical benefits, including a reduced risk of ArLD, lower rates of hepatic decompensation, and improved survival.1

According to the World Health Organization, an estimated 400 million people, or 7% of the global population ≥ 15 years of age, lived with alcohol use disorders in 2019. Access to screening, brief intervention, and treatment for people with hazardous alcohol use and AUD remains low, as does access to medications for the treatment of AUD, although effective treatments are limited.2

“The clinical impact of GLP-1RAs on patients with AUD remains unclear. Given that GLP-1RAs have been associated with reduced alcohol consumption, and exhibit pleiotropic effects, including cardiovascular, renal, and liver benefits, in addition to glycemic and body weight control, we hypothesize that GLP-1RAs may improve clinical outcomes in patients with AUD,” Chih-Cheng Lai, of the college of medicine at National Sun Yat-Sen University in Taiwan, and colleagues wrote.1

To investigate the association between GLP-1RAs and clinical outcomes in this patient population, investigators conducted 2 retrospective cohort studies using the TriNetX Research Network to identify adult patients ≥ 18 years of age with AUD or ArLD and type 2 diabetes who initiated either GLP-1RAs or DPP-4is between January 2010 and December 2023.1

The first cohort included patients with AUD and type 2 diabetes, while the second cohort included individuals with ArLD and type 2 diabetes. Patients from both cohorts were then stratified into GLP-1RA and DPP-4i groups based on their index prescription.1

Of note, individuals who had received medications from the opposing group within 6 months before or at any point after the index date were excluded. Additionally, all patients were required to have a minimum follow-up period of 1 month after cohort entry, which continued until the occurrence of outcomes, death, or the end of the study period in October 2024.1

Investigators employed propensity score matching with a 1:1 ratio to balance the GLP-1RA and DPP-4i groups within each cohort.1

For the AUD cohort, the primary outcome was the occurrence of ArLD during the follow-up period, while the secondary outcome was all-cause mortality. For the ArLD cohort, the primary outcome was the occurrence of hepatic decompensation, defined as variceal bleeding, hepatic encephalopathy, and ascites-related complications such as ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome. Secondary outcomes included hepatocellular carcinoma, liver transplant, and all-cause mortality.1

AUD Cohort Findings

From an initial population of 377,146 adult patients diagnosed with both AUD and type 2 diabetes, 33,658 patients received treatment with either GLP-1RA or DPP-4i during the study period. Of these, 11,368 patients were eligible for inclusion in the study and divided into 2 groups: the GLP-1RA group (n = 6114) and the DPP-4i group (n = 5254).1

During a median follow-up of 63.2 (interquartile range [IQR], 33.3–120) months, GLP-1RA users had a significantly lower risk of ArLD than DPP-4i users (incidence rate, 6.0 vs 8.7 per 1000 person-years; hazard ratio [HR], 0.62; 95% CI, 0.44–0.87; log-rank P = .006). Additionally, investigators noted GLP-1RA use was associated with a reduced risk of all-cause mortality (HR, 0.53; 95% CI, 0.45–0.62).1

ArLD Cohort Findings

From an initial population of 100,268 adult patients with concurrent diagnoses of ArLD and type 2 diabetes, 8318 patients received either GLP-1RA or DPP-4i during the study period. Of these, 3558 patients met the study inclusion criteria and were stratified into 2 groups: the GLP-1RA group (n = 1577) and the DPP-4i group (n = 1981).1

During a median follow-up of 28.2 (IQR, 33.3–51.7) months, GLP-1RA users had a significantly lower risk of hepatic decompensation than DPP-4i users (incidence rate, 39.5 vs 51.4 per 1000 person-years; HR, 0.66, 95% CI: 0.51–0.85; log-rank P = .001). Additionally, investigators pointed out GLP-1RA use was associated with a reduced risk of all-cause mortality (HR, 0.53; 95% CI, 0.41–0.68) but noted no significant differences were observed between the groups for the risk of hepatocellular carcinoma (HR, 0.93; 95% CI, 0.52–1.66) or liver transplant (HR, 1.22; 95% CI, 0.52–2.83).1

“These findings suggest that GLP-1RA could be a promising therapeutic option for patients with co-existing AUD and type 2 diabetes, particularly given the limited pharmacological treatments currently available for AUD,” investigators concluded.1 “While alcohol abstinence remains the cornerstone of AUD/ArLD management, GLP-1RA may offer additional benefits in reducing disease progression and mortality.”

References

1. Kuo CC, Li CH, Chuang MH, et al. Impact of GLP-1 Receptor Agonists on Alcohol-Related Liver Disease Development and Progression in Alcohol Use Disorder. Alimentary Pharmacology and Therapeutics. https://doi.org/10.1111/apt.70007
2. World Health Organization. Alcohol. June 28, 2024. Accessed February 6, 2025. https://www.who.int/news-room/fact-sheets/detail/alcohol