What is already known on this topic Preclinical studies suggest glucagon-like peptide-1 (GLP-1) receptor agonists act on the mesolimbic reward pathways and reduce drug reinforcement in animal models of alcohol, nicotine, cocaine, and opioid use disorders Observational studies in humans link GLP-1 receptor agonist use to lower risk of incident and recurrent alcohol, tobacco, and cannabis use disorders, but evidence for other substances is lacking Large studies evaluating GLP-1 receptor agonists for preventing substance use disorders (SUDs) or improving hard clinical outcomes in people with established SUDs are lacking What this study adds GLP-1 receptor agonists were associated with lower risks of incident alcohol, cannabis, cocaine, nicotine, opioid, and other SUDs, suggesting potential preventive effects across a broad range of substances In participants with pre-existing SUDs, GLP-1 receptor agonists were associated with reduced risks of SUD related emergency department visits, hospital admissions, and mortality, and drug overdoses and suicidal behaviours Ethics statements Ethical approval This study was approved by the institutional review board of the VA St Louis Health Care System, which granted a waiver of informed consent (protocol No 1606333)
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