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Observational Study
. 2025 Jan 1;82(1):94-98.
doi: 10.1001/jamapsychiatry.2024.3599.

Repurposing Semaglutide and Liraglutide for Alcohol Use Disorder

Markku Lähteenvuo  1 , Jari Tiihonen  1   2   3 , Anssi Solismaa  4   5 , Antti Tanskanen  1   2 , Ellenor Mittendorfer-Rutz  2 , Heidi Taipale  1   2   3   6
Affiliations
Observational Study

Repurposing Semaglutide and Liraglutide for Alcohol Use Disorder

Markku Lähteenvuo et al. JAMA Psychiatry. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Lähteenvuo reported personal fees from Janssen, Janssen-Cilag, Lundbeck, Otsuka Pharma, Recordati, and Sunovion Pharma outside the submitted work. Dr Tiihonen reported grants paid to their institution from Janssen-Cilag and consulting fees from HLS Therapeutics, Janssen, Orion, and WebMed Global outside the submitted work. Dr Tanskanen reported fees paid to their institution from Janssen outside the submitted work. Dr Taipale reported personal fees from Gedeon Richter, Janssen, Lundbeck, and Otsuka and grants from Janssen outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Risk of Hospitalization Due to Alcohol Use Disorder (AUD) and Substance Use Disorder (SUD)
The use of individual glucagon-like peptide-1 receptor (GLP-1) agonists was compared with nonuse of GLP-1 agonists. Groupwise and use of specific AUD medications were compared with nonuse of AUD medications. Both of these models (A and B) were adjusted for time-varying use of psychotropic medications (antipsychotics, N05A; antidepressants, N06A; mood stabilizers, including carbamazepine, N03AF01; valproic acid, N03AG01; lamotrigine, N03AX09; and lithium, N05AN01), benzodiazepines and related drugs (N05BA, N05CD, N05CF), and attention-deficit/hyperactivity disorder (ADHD) medications (N06BA); use of antidiabetic drugs other than GLP-1 agonists (A10 excluding A10BJ); temporal order of GLP-1 medication; and time since cohort entry. aHR indicates adjusted hazard ratio.
Figure 2.
Figure 2.. Risk of Hospitalization Due to Somatic Reasons and Suicide Attempt
The use of individual glucagon-like peptide-1 receptor (GLP-1) agonists was compared with nonuse of GLP-1 agonists. Groupwise and use of specific alcohol use disorder (AUD) medications were compared with nonuse of AUD medications. Both of these models (A and B) were adjusted for time-varying use of psychotropic medications (antipsychotics, N05A; antidepressants, N06A; mood stabilizers, including carbamazepine, N03AF01; valproic acid, N03AG01; lamotrigine, N03AX09; and lithium, N05AN01), benzodiazepines and related drugs (N05BA, N05CD, N05CF), and attention-deficit/hyperactivity disorder medications (N06BA); use of antidiabetic drugs other than GLP-1 agonists (A10 excluding A10BJ); temporal order of GLP-1 medication; and time since cohort entry. aHR indicates adjusted hazard ratio.
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References

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