Repurposing Semaglutide and Liraglutide: A New Hope for Alcohol Use Disorder

Exploring the potential of diabetes medications in treating alcohol addiction.

Alcohol Use Disorder (AUD) affects millions of people worldwide, leading to severe health complications, social problems, and economic burdens. Traditional treatments for AUD often focus on psychosocial interventions and a limited number of approved medications. However, recent research suggests that certain medications used to treat type 2 diabetes and obesity may offer new hope for individuals struggling with alcohol addiction. Specifically, glucagon-like peptide-1 (GLP-1) receptor agonists like semaglutide and liraglutide have shown promise in reducing alcohol consumption.

Understanding GLP-1 Receptor Agonists

GLP-1 receptor agonists are a class of medications that mimic the action of the GLP-1 hormone, which is involved in regulating blood sugar levels and appetite. These medications are primarily used to manage type 2 diabetes and promote weight loss by:

• Stimulating insulin secretion
• Suppressing glucagon release
• Slowing gastric emptying
• Reducing appetite

Common GLP-1 Agonists:

• Semaglutide (brand names: Ozempic®, Wegovy®)
• Liraglutide (brand names: Victoza®, Saxenda®)

Recent studies have indicated that GLP-1 receptors are also present in areas of the brain associated with reward and addiction pathways. This discovery has led researchers to explore the potential of GLP-1 agonists in treating AUD.

The Study at a Glance

A comprehensive observational study was conducted to investigate whether GLP-1 receptor agonists could reduce the risk of hospitalization due to AUD. Here’s how the study was structured:

Study Design:

• Type: Nationwide observational cohort study
• Location: Sweden
• Duration: January 2006 to December 2023
• Participants:227,866 individuals aged 16 to 64 diagnosed with AUD
  • Gender Breakdown: 63.5% male, 36.5% female
  • Average Age: 40 years
• Median Follow-Up Time: 8.8 years

Medications Examined:

• Primary Focus: Semaglutide and Liraglutide
• Comparison Medications: Other GLP-1 agonists (Exenatide, Dulaglutide) and approved AUD medications (Disulfiram, Acamprosate, Naltrexone) The existing medication approved for AUD will likely need their own article to be explained.

Methodology

Data Collection:

• Researchers utilized Sweden’s national health registers, including inpatient care, specialized outpatient care, and prescription data.
• Individual medication usage was tracked using the PRE2DUP method, which constructs drug use periods based on prescription records.

Exposure Assessment:

• Primary Exposure: Use of GLP-1 agonists (Semaglutide, Liraglutide)
• Secondary Exposure: Use of medications officially approved for AUD

Outcome Measures:

• Primary Outcome: Hospitalization due to AUD
• Secondary Outcomes:
  • Hospitalization due to any Substance Use Disorder (SUD)
  • Hospitalization for somatic (physical) reasons
  • Hospitalization due to suicide attempts

Statistical Analysis:

• A within-individual design was employed, comparing periods when individuals were on medication versus when they were not.
• Adjusted Hazard Ratios (aHRs) were calculated to assess the risk of hospitalization associated with medication use.
  • An aHR less than 1 indicates a reduced risk.
• Confidence Intervals (CIs) provided a range in which the true effect likely falls with 95% certainty.

Dosages and Durations

While the study did not specify exact dosages for AUD treatment, typical dosing for these medications in diabetes and obesity management is as follows:

• Semaglutide:
  • Starting Dose: 0.25 mg once weekly
  • Maintenance Dose: Up to 1 mg weekly for diabetes; up to 2.4 mg weekly for weight management
  • Administration: Subcutaneous injection
• Liraglutide:
  • Starting Dose: 0.6 mg daily
  • Maintenance Dose: 1.2 mg to 1.8 mg daily for diabetes; up to 3 mg daily for weight management
  • Administration: Subcutaneous injection

Participants’ medication use was tracked over the median follow-up period of 8.8 years, allowing researchers to observe long-term effects. When analyzing the data below, there are a lot of technical biostatistics, which may overwhelm the reader, but what is important is that all results mentioned here are statistically significant. The highlighted yellow data is the most crucial number to show how quantitatively Ozempic (Semaglutide)  and Victoza (Liraglutide) help in AUD and SUD.

Key Findings

1. Reduced Risk of AUD Hospitalization
   • Semaglutide Users:
     • 36% reduction in the risk of hospitalization due to AUD
     • Adjusted Hazard Ratio (aHR): 0.64
     • Confidence Interval (CI): 0.50 to 0.83
   • Liraglutide Users:
     • 28% reduction in hospitalization for AUD 
     • aHR: 0.72
     • CI: 0.57 to 0.92
2. Interpretation: An aHR of 0.64 means that semaglutide users had a 36% lower risk of AUD hospitalization compared to when they were not using the medication.
3. Reduced Risk of SUD Hospitalization
   • Semaglutide Users:
     • 32% reduction in hospitilzation for SUD
     • aHR: 0.68
     • CI: 0.54 to 0.85
   • Liraglutide Users:
     • 22% reduction
     • aHR: 0.78
     • CI: 0.64 to 0.97
4. Reduced Risk of Somatic Hospitalizations
   • Semaglutide Users:
     • 22% reduction in hospitalization for Somatic Symptoms
     • aHR: 0.78
     • CI: 0.68 to 0.90
   • Liraglutide Users:
     • 21% reduction
     • aHR: 0.79
     • CI: 0.69 to 0.91

Discussion

The study demonstrated that among individuals with AUD, the use of semaglutide and liraglutide was associated with a significantly reduced risk of hospitalization due to AUD and SUD. Specifically, semaglutide users had a 36% lower risk of AUD hospitalization, while liraglutide users had a 28% lower risk compared to periods of non-use.

The use of semaglutide and liraglutide was also associated with a decreased risk of somatic hospitalizations, suggesting potential broader health benefits beyond AUD management.

Contribution to the Body of Knowledge

This study adds to the growing body of evidence that GLP-1 agonists may have therapeutic benefits beyond glycemic control and weight management. It is one of the largest real-world analyses demonstrating the association between GLP-1 agonist use and reduced AUD-related hospitalizations. The within-individual design strengthens the validity of the findings by minimizing confounding factors. There is another study that showed similar results based on social media posts. It is important to understand that researchers often repeat smaller, more informal studies with larger and more rigorous studies to confirm robustness of evidence. Researchers would like to have evidence that their conclusion will be true before investing time and money into researching random hypotheses. 

Understanding the Statistics

• Adjusted Hazard Ratio (aHR): A statistical measure used to compare the risk of an event occurring between two groups over time. The adjusted part of the Hazard Ratio means that the researchers had to analyze the data and attempt to compare it to the same patient’s overall characteristics concerning addiction to make a more accurate inference. For example, drug A is supposed to be twice as effective as drug B in treating AUD, but if the study gave drug A to alcoholics with four times more severe AUD, then the researchers may reach an incorrect conclusion. The severity of addiction was one specific example, but in fact, researchers also try to match as many other variables as possible, such as age and comorbidities.

• aHR < 1: Indicates a reduced risk
  • aHR = 1: No difference in risk
  • aHR > 1: Indicates an increased risk
• Confidence Interval (CI): Provides a range within which the true effect size is likely to fall.
  • If the CI does not include 1, the result is considered statistically significant. If the CI included 1 or went above 1 it would mean there is a lower than 95% chance that a result is real assuming the standard p value threshold of .05.
  • Narrower CIs indicate more precise estimates.

Example: An aHR of 0.64 with a 95% CI of 0.50 to 0.83 means there is a statistically significant 36% reduction in risk, and we can be 95% confident the true aHR falls between 0.50 and 0.83.

Why These Results Are Significant

1. Potential for Repurposing Medications
   • The study suggests that semaglutide and liraglutide could be effective treatments for AUD, providing a new therapeutic avenue.
2. Greater Efficacy Compared to Existing Treatments
   • The reductions in hospitalization risk were more pronounced with GLP-1 agonists than with medications currently approved for AUD.
3. Dual Health Benefits
   • These medications could simultaneously manage type 2 diabetes or obesity and reduce alcohol consumption, benefiting overall health.
4. Mechanism of Action
   • By acting on GLP-1 receptors in the brain’s reward pathways, these medications may reduce cravings and the reinforcing effects of alcohol.

Limitations of the Study

• Observational Nature: Cannot definitively establish causality; randomized controlled trials are needed.
• Medication Adherence: Prescription data may not accurately reflect whether patients took the medication as prescribed.
• Lack of Specific Dosage Information for AUD: Dosages used for AUD treatment were not specified.
• Population Specificity: Findings are based on a Swedish population and may not be generalizable globally.

Implications for Patients and Healthcare Providers

For Patients:

• Individuals with AUD, especially those with type 2 diabetes or obesity, may benefit from discussing GLP-1 agonists with their healthcare providers.
• These medications could address multiple health concerns simultaneously.

For Healthcare Providers:

• Awareness of emerging treatments is crucial.
• Consideration of GLP-1 agonists as part of a comprehensive treatment plan for patients with AUD and metabolic conditions.

Future Directions

• Randomized Controlled Trials: Necessary to confirm these findings and establish appropriate dosing for AUD treatment.
• Further Research: Explore the mechanisms by which GLP-1 agonists affect alcohol consumption.
• Broader Applications: Investigate the potential benefits for other substance use disorders.

Conclusion

The study highlights a promising new use for Semaglutide and liraglutide in treating Alcohol Use Disorder and Substance Use Disorder. It should not be surprising that Ozempic has slightly better results than Victoza because Ozempic binds to the GLP-1 Receptor more strongly than Victoza. Ozempic in general is considered a newer and better GLP-1RA than Victoza.

Disclaimer: This article is for informational purposes only and does not substitute professional medical advice. Always consult a qualified healthcare provider for guidance tailored to your health situation.

At BorderFreeHealth, we’re dedicated to providing up-to-date information and quality medications to support your health needs. Explore our range of GLP-1 receptor agonists and consult with our pharmacists for more information.