01. Can GLP-1 Agonists Treat Alcohol Use Disorder?

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GLP-1 Receptor Agonists: Promising AUD Treatment

Today, I’d like to discuss an exciting potential new treatment for alcohol use disorder (AUD).

Current AUD Medications: Limited Efficacy

We currently have three FDA-approved medications for AUD:

• Disulfiram (approved in 1951)
• Acamprosate
• Naltrexone

Unfortunately, none of these medications is broadly effective or widely used. Disulfiram has very little use due to severe, potentially life-threatening side effects if taken with alcohol.

Acamprosate and naltrexone have better safety profiles and tolerability but only modest efficacy.

GLP-1 Receptor Agonists: A New Hope

Given the limitations of current treatments, there’s considerable excitement about a new class of medication: glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists).

The major medications in this class are:

• Semaglutide (brand names Ozempic and Wegovy)
• Liraglutide (brand name Saxenda)

Currently, semaglutide is FDA approved for type 2 diabetes and weight loss, while liraglutide is approved only for weight loss. Neither is FDA approved for AUD.

Evidence Supporting GLP-1 Receptor Agonists

Interest in these medications stems from two lines of evidence:

1. Studies in rodents and monkeys found that GLP-1 receptor agonists significantly reduced alcohol intake.
2. Some patients taking GLP-1 receptor agonists for weight loss report significantly reduced alcohol cravings.

Real-World Evidence: Swedish Study

A study by Lahteenvuo and colleagues provides real-world evidence supporting the potential of GLP-1 receptor agonists for AUD treatment. The researchers utilized Sweden’s comprehensive population-based registries to study 227,000 individuals with alcohol-related disorders, including almost 8,000 prescribed a GLP-1 receptor agonist.

Of those prescribed GLP-1 receptor agonists:

• 54% received semaglutide
• 31% received liraglutide
• 15% received other GLP-1 receptor agonists

Significant Reduction in Alcohol-Related Hospitalizations

The study found that patients prescribed a GLP-1 receptor agonist had a significant one-third lower risk of hospitalization for alcohol-related disorders during periods they were taking the medication compared to periods when they were not.

This comparison statistically controlled for prescriptions of psychotropic or anti-diabetes medications.

In contrast, prescription of an approved AUD medication (acamprosate, disulfiram, or naltrexone) was associated with only a modest 2% reduction in hospitalization risk.

Study Strengths: Population-Based Design

This study has several methodological strengths that increase my confidence in its findings. The availability of data covering essentially the entire national population over the follow-up period largely eliminates bias from sampling procedures and participant dropout.

Another strength is the sophisticated within-participant design. Each participant served as their own control, comparing time periods when they were using the medication versus periods when they were not. This eliminates confounding by differences in sociodemographic or clinical characteristics among participants.

Study Limitations: Population and Diagnosis

The study does have limitations. The Swedish population lacks the racial and ethnic diversity found in the US population, with only 6% of study participants reporting non-European ancestry.

Another limitation is the reliance on diagnoses appearing in medical records, which may not be as accurate as those made in research settings by trained staff. Additionally, the study used a broad definition of alcohol-related disorders, not restricted to AUD alone.

Future Research and Clinical Implications

While GLP-1 receptor agonists show promise as a treatment for AUD, several years of further drug development effort remain before we can hope to see them FDA approved and available for clinical use.

This effort must include phase 2 and phase 3 randomized, placebo-controlled clinical trials (RCTs) to evaluate the safety, efficacy, and tolerability of these medications in patients without diabetes or weight management problems.

Caution Advised for Off-Label Use

In the meantime, physicians should be very cautious when considering prescribing these medications off-label. Personally, I would not consider using a GLP-1 receptor agonist unless the patient had clearly not responded well to one or more FDA-approved AUD medications.

Thank you for listening to this Quick Take on the potential of GLP-1 receptor agonists in the treatment of alcohol use disorder.

Abstract

Repurposing Semaglutide and Liraglutide for Alcohol Use Disorder
Markku Lähteenvuo, M.D, Ph.D.; Jari Tiihonen, M.D, Ph.D.; Anssi Solismaa, M.D, Ph.D.; et al.

Importance Preliminary studies suggest that glucagon-like peptide-1 receptor (GLP-1) agonists, used to treat type 2 diabetes and obesity, may decrease alcohol consumption.

Objective To test whether the risk of hospitalization due to alcohol use disorder (AUD) is decreased during the use of GLP-1 agonists compared with periods of nonuse for the same individual.

Design, Setting, and Participants This cohort study was an observational study conducted nationwide in Sweden using data from January 2006 to December 2023. The population-based cohort was identified from registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. Participants were all residents aged 16 to 64 years who had a diagnosis of AUD.

Exposures The primary exposure was use of individual GLP-1 agonists (compared with nonuse of GLP-1 agonists), and the secondary exposure was medications with indication for AUD.

Main Outcomes and Measures The primary outcome was AUD hospitalization, analyzed in a Cox regression within-individual model. Secondary outcomes were any substance use disorder (SUD)–related hospitalization, somatic hospitalization, and suicide attempt.

Results The cohort included 227 866 individuals with AUD; 144 714 (63.5%) were male and 83 154 (36.5%) were female, with a mean (SD) age of 40.0 (15.7) years. Median (IQR) follow-up time was 8.8 (4.0-13.3) years. A total of 133 210 individuals (58.5%) experienced AUD hospitalization. Semaglutide (4321 users) was associated with the lowest risk (AUD: adjusted hazard ratio [aHR], 0.64; 95% CI, 0.50-0.83; any SUD: aHR, 0.68; 95% CI, 0.54-0.85) and use of liraglutide (2509 users) with the second-lowest risk (AUD: aHR, 0.72; 95% CI, 0.57-0.92; any SUD: aHR, 0.78; 95% CI, 0.64-0.97) of both AUD and SUD hospitalization. Use of any AUD medication was associated with a modestly decreased risk (aHR, 0.98; 95% CI, 0.96-1.00). Semaglutide (aHR, 0.78; 95% CI, 0.68-0.90) and liraglutide (aHR, 0.79; 95% CI, 0.69-0.91) use were also associated with decreased risk of somatic hospitalizations but not associated with suicide attempts (semaglutide: aHR, 0.55; 95% CI, 0.23-1.30; liraglutide: aHR, 1.08; 95% CI, 0.55-2.15).

Conclusions and Relevance Among patients with AUD and comorbid obesity/type 2 diabetes, the use of semaglutide and liraglutide were associated with a substantially decreased risk of hospitalization due to AUD. This risk was lower than that of officially approved AUD medications. Semaglutide and liraglutide may be effective in the treatment of AUD, and clinical trials are urgently needed to confirm these findings.

Reference

Lähteenvuo, M. M.D, Ph.D.; Tiihonen, J. M.D, Ph.D.; Solismaa, A. M.D, Ph.D.; et al. (2024).

Repurposing Semaglutide and Liraglutide for Alcohol Use Disorder

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JAMA Psychiatry

. 2025;82(1):94-98.