GLP-1 drugs, like semaglutide, lower risk of hospitalizations for alcohol use disorder

By Dr. Chinta SidharthanReviewed by Danielle Ellis, B.Sc.Nov 18 2024

A long-term study suggests GLP-1 agonists, especially semaglutide, may lower the risk of alcohol use disorder hospitalizations, highlighting the potential for novel treatments pending further clinical trials.

In a recent study published in JAMA Psychiatry, a team of researchers from Europe investigated whether glucagon-like peptide-1 receptor (GLP-1) agonists, which are primarily used to treat diabetes and obesity, could be used to reduce alcohol use disorder (AUD)-related hospitalizations.

They analyzed Swedish registry data and evaluated whether GLP-1 agonists, particularly liraglutide and semaglutide, could offer new avenues for mitigating the adverse impacts of AUD.

Background

Alcohol use disorder contributes significantly to the global disease burden, and although various psychosocial and pharmacological treatment options for AUD are available, they are often under-utilized. Furthermore, existing medications for AUD, such as disulfiram, naltrexone, and acamprosate, demonstrate varying efficacy, highlighting the need for alternative therapeutic options.

Recent findings suggest that GLP-1 agonists, which are widely prescribed for diabetes and obesity, might influence alcohol consumption behaviors. Preclinical research in animals and observational studies in humans have linked GLP-1 receptor pathways to reduced cravings and lower alcohol intake, potentially mediated by dopamine modulation in reward mechanisms.

Furthermore, genetic associations between GLP-1 receptors and AUD indicate a biological overlap that warrants further examination. Although Danish registry studies have reported transient benefits from GLP-1 agonist use on alcohol-related outcomes, comprehensive data on long-term impacts and broader clinical effectiveness are limited.

About the study

In the present study, the researchers utilized the national registry data from Sweden to examine whether GLP-1 agonists could positively impact the risk of AUD-related hospitalizations. A cohort of over 200,000 individuals between the ages of 16 and 64 with an AUD diagnosis between 2006 and 2023 was identified from the registries, which provided data on inpatient care, outpatient visits, and social insurance.

The primary exposure examined in the study was GLP-1 agonist use, which included semaglutide, liraglutide, and others. This was compared to non-use of GLP-2 during the follow-up periods for the same individual. A secondary comparison examined the effects of medications approved for AUD, such as disulfiram, acamprosate, and naltrexone.

The primary outcome was AUD-related hospitalizations, which were analyzed using a Cox regression model with a within-individual design. This method controlled for confounding factors by comparing the same individuals during periods of medication use versus non-use. Additionally, secondary outcomes such as hospitalizations for substance use disorders, somatic conditions or intense physical symptoms due to emotional distress, and suicide attempts were also examined.

Furthermore, the researchers used statistical models to account for variables such as psychotropic medication use, antidiabetic treatments, and temporal factors. Hazard ratios (HR) were adjusted for confounders, providing a robust estimate of associations. Additionally, the study analyzed specific GLP-1 agonists and AUD medications individually, and the results for AUD medications were aggregated for comparison.

Results

The researchers found that the use of GLP-1 agonists significantly reduced the risk of AUD-related hospitalizations compared to periods of non-use within the same individuals. Among the various medications analyzed, semaglutide showed the most substantial impact, with an adjusted HR of 0.64 for AUD-related hospitalizations and 0.68 for substance use disorder-related hospitalizations. Liraglutide was associated with similar beneficial effects, demonstrating an adjusted HR of 0.72 for AUD and 0.78 for substance use disorder-related hospitalizations.

In comparison, traditional AUD medications cumulatively provided only a modest reduction in the risk for AUD-related hospitalizations, with an adjusted HR of 0.98. However, specific AUD treatments displayed relatively better outcomes within this group.

Naltrexone demonstrated the most notable reduction in hospitalization risk, with an adjusted HR of 0.86 for both AUD- and substance use disorder-related hospitalizations. Although disulfiram and acamprosate provided more modest effects, their effectiveness was comparatively limited when evaluated against the stronger impacts of semaglutide and liraglutide.

Furthermore, examination of the secondary outcomes reported that semaglutide and liraglutide were linked to reduced risks of hospitalizations for somatic conditions, with liraglutide and semaglutide showing an adjusted HR of 0.79 and 0.78, respectively. However, these medications did not demonstrate statistically significant changes in suicide attempt risks, though the adjusted HR for semaglutide indicated promise.

Interestingly, the tested GLP-1 agonists outperformed the traditional AUD medications in reducing AUD-related hospitalization risks, highlighting their potential as a novel treatment approach. These results also aligned with emerging preclinical data that indicate GLP-1 receptor involvement in reward pathways as a potential mitigating factor for alcohol cravings and consumption.

Conclusions

Overall, the study suggested that GLP-1 agonists, particularly liraglutide and semaglutide, were promising options for reducing AUD-related hospitalizations. Their superior performance over traditional AUD medications also highlighted the potential for broader therapeutic applications, such as the treatment of somatic symptom disorder and substance use disorders. However, the researchers emphasized that randomized clinical trials were imperative to confirm these findings and establish their role in AUD treatment frameworks.