Efficacy of the GLP-1 receptor agonist, semaglutide, in abstinence from illicit and nonprescribed opioids in an outpatient population with OUD: a randomized, double-blind, placebo-controlled clinical trial protocol.

BACKGROUND: Standard medications for opioid use disorder (MOUD) provide effective treatment pathways for recovery compared with no treatment or behavioral therapies alone. That said, people who continue to use non-prescribed opioids despite treatment with MOUD are at greater risk for high attrition and OUD-related harms. Novel, more effective approaches are needed for the treatment of OUD. To that end, glucagon-like peptide-1 receptor agonists (GLP-1RAs) provide a promising option as a non-opioid pharmacological intervention for OUD. Observational studies suggest that GLP-1RAs decrease craving measures in a residential OUD population but no controlled clinical trials have been conducted to determine if GLP-1RAs increase opioid abstinence and reduce craving in individuals with OUD in an outpatient population. The purpose of the current protocol is to evaluate the potential for the GLP-1RA, semaglutide, to increase abstinence and reduce craving in an outpatient population enrolled in a MOUD program and continue to use non-prescribed opioids. METHOD: This protocol is a randomized, double-blind, placebo-controlled clinical trial designed to test the efficacy of the GLP-1RA, semaglutide, in 200 participants enrolled in an outpatient MOUD program (n = 100 buprenorphine; n = 100 methadone) for the treatment of OUD. Outcomes include the probability of participants being abstinent from illicit and nonprescribed opioids, as well as measures of craving and days of drug use. Measures will be evaluated using urine toxicology screens and self-report assessments across 19 weeks during a screening visit (Study Week 1), 12 treatment visits (Study Weeks 2-13), a washout visit (Study Week 14), and a final follow-up visit (Study Week 19). DISCUSSION: This manuscript describes a phase II clinical protocol to collect data on the efficacy of a GLP-1RA, semaglutide, in persons enrolled in an MOUD program and with ongoing non-prescribed opioid use despite treatment with methadone or buprenorphine. Completion of the current project will support the feasibility of phase III clinical trials for further evaluation in larger outpatient OUD populations that may lead to a new indication for GLP-1RA as a novel and effective treatment for OUD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06548490. Registered 12 August 2024, https://clinicaltrials.gov/study/NCT06548490 .