Journal of dual diagnosisAug 24, 2026

Potential of GLP-1 Receptor Agonists and DPP4 Inhibitors in Treating Opioid Addiction

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 25, 2026

Abstract

A total of 21 studies were included in the review of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors for opioid use disorder.

Thirteen pre-clinical studies indicated that incretin-based medications may reduce opioid-seeking and self-administration behaviors in rodents.
Four observational studies suggested that glucagon-like peptide-1 receptor agonists, particularly semaglutide, could be linked to reduced opioid overdose and substance use.
One published randomized controlled trial and three ongoing trials are currently investigating the effects of these medications on overdose, cravings, and treatment retention.
Preliminary findings indicate that glucagon-like peptide-1 receptor agonists may be associated with positive neuropsychiatric outcomes related to opioid use disorder.
Further research is needed to fully understand the role of these medications, particularly in combination with opioid agonist therapy.

Simplified

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.

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Potential of GLP-1 Receptor Agonists and DPP4 Inhibitors in Treating Opioid Addiction

Abstract

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