Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population – Nature Communications

Abstract

Alcohol use disorders (AUD) significantly contribute to the global burden of disease, yet treatment options are limited. Semaglutide, a medication for obesity and type 2 diabetes (T2DM), has shown potential in reducing alcohol consumption. This retrospective cohort study analyzed electronic health records of 83,825 patients with obesity and 598,803 patients with T2DM. Results indicate that semaglutide is associated with a 50%-56% lower risk of both incidence and recurrence of AUD over a 12-month period, regardless of gender, age, race, or T2DM status. These findings suggest semaglutide’s potential benefits for AUD and call for further clinical trials.

Introduction

Approximately 29.5 million Americans aged 12 and older had an AUD in 2021. AUD is responsible for over 80,000 deaths annually in the USA and ranks among the top 10 conditions for global disease burden. Current medications approved by the FDA and EMA offer modest therapeutic benefits, highlighting the need for new treatments. Reports of reduced drinking in patients treated with GLP-1RA medications for T2DM or obesity have sparked interest in these medications as potential treatments for AUD. Semaglutide, in particular, has shown promising results in reducing alcohol intake and relapse in animal studies and anecdotal patient reports.

Study Populations

Obesity Cohort

The study included 83,825 patients with obesity who had no prior diagnosis of AUD and were newly prescribed semaglutide or other anti-obesity medications between June 2021 and December 2022.

T2DM Cohort

The study also analyzed data from 598,803 patients with T2DM who had no prior diagnosis of AUD and were newly prescribed semaglutide or non-GLP-1RA anti-diabetes medications between December 2017 and May 2021.

Results

Incidence of AUD in Obesity Cohort

• The semaglutide cohort showed a significantly lower risk of incident AUD diagnosis compared to the non-GLP-1RA anti-obesity medications cohort.
• Reductions were consistent across gender, age group, race, and T2DM status.

Recurrence of AUD in Obesity Cohort

• Patients with a prior history of AUD treated with semaglutide also showed a significantly lower risk of recurrent AUD diagnosis.
• This finding was consistent across demographic groups and T2DM status.

Incidence and Recurrence of AUD in T2DM Cohort

• In the T2DM cohort, semaglutide was associated with a lower risk of both incident and recurrent AUD diagnosis.
• The lower risk associations persisted for up to 3 years of follow-up.

Discussion

The study provides evidence supporting the potential therapeutic benefits of semaglutide for AUD in real-world populations. The mechanisms may involve modulation of the brain dopamine reward system and stress responses. However, randomized clinical trials are necessary to confirm these findings and assess semaglutide’s effects on mood and suicidal ideation.

Methods

Database

The TriNetX Analytics Platform was used to analyze de-identified patient electronic health records from various healthcare organizations.

Ethics Statement

The study used HIPAA de-identified data, hence IRB approval was not required.

Data Availability

Data specific to this study is included in the manuscript as tables, figures, and supplementary files. Access to the full dataset from TriNetX may incur costs and require a data-sharing agreement.

Code Availability

All statistical analyses were performed using built-in functions within the TriNetX Analytics Platform. Data and code to recreate figures are available on GitHub.

Acknowledgements

The study was supported by the National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Cancer Institute Case Comprehensive Cancer Center.

Author Information

1. William Wang & Nathan A. Berger – Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, OH, USA
2. Nora D. Volkow – National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA
3. Pamela B. Davis – Center for Community Health Integration, Case Western Reserve University School of Medicine, Cleveland, OH, USA
4. David C. Kaelber – Center for Clinical Informatics Research and Education, The MetroHealth System, Cleveland, OH, USA
5. Rong Xu – Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, OH, USA

Ethics Declarations

The authors declare no competing interests.

Peer Review Information

Nature Communications thanks Sanjay Kalra and anonymous reviewers for their contribution to the peer review of this work.

Supplementary Information

Supplementary information is available for this paper.

Source Data

Source data are provided with this paper.

Rights and Permissions

This article is licensed under a Creative Commons Attribution 4.0 International License.

About this Article

Cite this article as: Wang et al., Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population. Nat Commun, 15:4548 (2024).

Which SDGs are addressed or connected to the issues highlighted in the article?

1. SDG 3: Good Health and Well-being

What specific targets under those SDGs can be identified based on the article’s content?

1. Target 3.4: By 2030, reduce by one third premature mortality from non-communicable diseases through prevention and treatment and promote mental health and well-being.
2. Target 3.5: Strengthen the prevention and treatment of substance abuse, including narcotic drug abuse and harmful use of alcohol.

Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

• Indicator for Target 3.4: The incidence and recurrence rates of alcohol use disorder (AUD) in patients treated with semaglutide compared to other medications.
• Indicator for Target 3.5: The reduction in the desire to drink alcohol reported by patients treated with semaglutide.

Create a table with three columns titled ‘SDGs, Targets and Indicators’ to present the findings from analyzing the article.

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