Glucagon-like peptide-1 receptor agonists for the treatment of opioid use disorders: a systematic review.

INTRODUCTION: Extant literature indicated that glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may potentially reduce risk of opioid overdose in persons with opioid use disorders (OUDs). Herein, we conducted a comprehensive synthesis of the effects of GLP-1 and GLP-1 RAs on OUDs. METHODS: We examined preclinical and clinical paradigms examining the effects of GLP-1 and GLP-1 RAs on OUD and OUD-associated behaviours (i.e. opioid self-administration, opioid-seeking behaviour). Relevant articles were retrieved from OVID (MedLine, Embase, AMED, PsychINFO, and JBI EBP Database), PubMed, and Web of Science from database inception to 1 May 2025. Primary studies ( = 10) examining the aforementioned effects associated with GLP-1 and GLP-1 RA administration were retrieved for analysis. RESULTS: GLP-1 RAs (i.e. exenatide, liraglutide) reduced opioid-seeking behaviour ( < 0.05) and self-administration of opioid drugs ( < 0.05) in preclinical paradigms. In addition, results from human studies indicate that GLP-1 administration was associated with reducing the risk of opioid overdose in human studies (aIRR = 0.60, 95% CI [0.43, 0.83]). CONCLUSION: GLP-1 RAs may affect opioid self-administration as well as the risk for overdose as evidenced by both preclinical and clinical data. There is a need for adequate well-controlled studies to determine whether GLP-1 RAs may provide clinically meaningful improvement and risk reduction in persons living with OUDs.