ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Addictive Disorders
Association Between GLP-1 Receptor Agonist Use and Substance Use Disorders Among Individuals with Type 2 Diabetes or Obesity: A Nested Case-Control Study in the All of Us Research Program
Tadesse M. Abegaz 1
Muktar Ahmed 2
Akshaya Bhagavathula 3
Gabriel Frietze 1
1. The University of Texas at El Paso School of Pharmacy, El Paso, United States
2. Flinders University College of Medicine and Public Health, Adelaide, Australia
3. North Dakota State University Press, Fargo, United States
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Abstract
Objectives: The current study evaluated the association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and substance use disorders (SUD) in type 2 diabetes and obesity. Methods: We conducted a retrospective nested case-control study using the All of Us Research Program data. Cases were defined as diabetes/obese individuals with a new diagnosis of alcohol use disorder (AUD), opioid use disorder (OUD), nicotine use disorder (NUD), or cocaine use disorder (CUD). Control participants were drawn from individuals with diabetes or obesity who had no documented history of SUD. Conditional logistic regression was performed to estimate the association between SUD and GLP-1 RA exposure. Results: The study included 22,652 participants with AUD, 13,226 with OUD, 42,320 with NUD, and 9,296 with CUD. GLP-1 RA use was associated with a 74% reduction in the odds of AUD (odds ratio [OR] = 0.26; 95% confidence interval [CI]: 0.20–0.34), a 69% reduction in the odds of OUD (OR = 0.31; 95% CI: 0.23–0.42), a 68% reduction in the odds of NUD (OR = 0.32; 95% CI: 0.27–0.39), a 75% reduction in the odds of CUD (OR = 0.25; 95% CI: 0.16–0.40), and 72% lower odds of any SUD compared with non-users participants (OR = 0.25, 95% CI 0.22–0.30).
Summary
Keywords
alcohol use, All of Us cohort, cocaine dependence, drug repurposing, GLP-1 receptor agonists, Nicotine dependence, Opioid use, substance use disorders
Received
13 December 2025
Accepted
18 February 2026
Copyright
© 2026 Abegaz, Ahmed, Bhagavathula and Frietze. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Tadesse M. Abegaz
Disclaimer
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