From metabolic therapy to addiction care: a clinical pharmacology roadmap for GLP-1 receptor agonists in substance use disorders

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), established treatments for type 2 diabetes and obesity, are being investigated for substance use disorders (SUDs). Randomized evidence is emerging in alcohol use disorder (AUD), while evidence for opioid, nicotine, cocaine, cannabis, and stimulant use disorders remains mixed, observational, or investigational. AREAS COVERED: This targeted narrative review integrates PubMed/MEDLINE literature, US Food and Drug Administration guidance and labeling, and ClinicalTrials.gov records available through 15 July 2026, with targeted literature and registry updates through 20 October 2026. It evaluates mechanistic plausibility, randomized and real-world human evidence, agent- and dose-specific pharmacology, co-treatment with established SUD medications, safety, adherence, benefit-risk assessment, harm reduction, equity, and trial design. EXPERT OPINION: The evidence is sufficient to justify indication-specific clinical development, especially for AUD, but currently insufficient for routine off-label treatment of SUDs for patients without an approved metabolic indication. Near-term research should test GLP-1 RAs as adjuncts rather than replacements for established SUD care, distinguish direct reward effects from weight loss and adverse-effect pathways, and embed risk minimization, patient-important outcomes, and equitable access into development from the outset.