Exploring The Role of GLP-1 Receptor Agonists and DPP4 Inhibitors in the Treatment of Opioid Use Disorder: A Scoping...

Background: Substance use disorders continue to cause significant morbidity and mortality. Of the drug use disorders, opioid use disorder is associated with the largest disease burden globally, however, the number of people treated with pharmacotherapy remains low. Emerging literature has highlighted incretin-based medications as potential novel treatments for opioid use disorder. This review aims to synthesize the current and upcoming literature on glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP4i) in this context. Methods: We searched the scientific databases PubMed, Embase, PsychINFO, ClinicalTrials.gov, and EuropePMC for pre-clinical and clinical studies analyzing effects of GLP-1 RA and DPP4i in opioid use disorder. Results were narratively synthesized. Results: Our search yielded 857 papers to screen, of which a total of 21 studies (preclinical, observational, and clinical trials - ongoing and completed) were included. There were 13 pre-clinical studies published, and most of these rodent studies found reduction in opioid-seeking and self-administration behaviors. Four observational studies suggest glucagon-like peptide-1 receptor agonists, especially semaglutide, may be associated with reduced opioid overdose, substance use, and other neuropsychiatric outcomes. Our search identified one published, preprint randomized controlled trial and three studies that are ongoing but not yet published. Ongoing randomized trials are examining effects on overdose, cravings, and treatment retention. Discussion: This review summarizes current evidence on GLP-1 RA and DPP4i in opioid use disorder. Retrospective observational data with GLP-1 RA have shown benefits. Controlled GLP-1 RA trials are ongoing, which are necessary for definitive conclusions, but preliminary findings suggest they may be associated with reductions in opioid-related outcomes. Further studies are needed to clarify their role, including its use alongside opioid agonist therapy.