Evidence map›Paper›PMID 41168808›Full record

ArticleAddiction science & clinical practice2025

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.

Christopher S Freet, Kirsten Shuler, Sarah Kawasaki, Eric Weintraub, Aaron Greenblatt, Mat Kladney, Edward Nunes, Katrina L Foster, Lan Kong, Nazia Raja-Khan and 5 more

Registry-linked trialAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Addiction science & clinical practice, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06548490 (GLP-1R Agonist Treatment for Opioid Use Disorder), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06548490 phase2recruitingnot on this map

GLP-1R Agonist Treatment for Opioid Use Disorder

TypeinterventionalSponsorMilton S. Hershey Medical CenterRan2025 to 2027Enrolled200ConditionsOpioid Use Disorder, Opioid Abuse and Addiction, Narcotic-Related Disorders, Substance-Related DisordersArmsSemaglutide Pen Injector, Placebo
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Christopher S FreetDepartment of Psychiatry and Behavioral Health, Penn State College of Medicine, Hershey, PA, USA.
Kirsten ShulerDepartment of Neuroscience and Experimental Therapeutics, Penn State College of Medicine, 500 University Drive, Hershey, PA, 17033, USA.
Sarah KawasakiDepartment of Psychiatry and Behavioral Health, Penn State College of Medicine, Hershey, PA, USA.
Eric WeintraubDepartment of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Aaron GreenblattDepartment of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Mat KladneyDepartment of Medicine, New York University Grossman School of Medicine, New York, NY, USA.
Edward NunesDivision of Substance Use Disorders, Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA.
Katrina L FosterNational Institute on Drug Abuse, Bethesda, MD, USA.
Lan KongDepartment of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.
Nazia Raja-KhanDepartment of Medicine, Penn State College of Medicine, Hershey, PA, USA.
H Harrington ClevelandDepartment of Human Development and Family Studies, Pennsylvania State University, University Park, PA, USA.
Patricia S GrigsonDepartment of Neuroscience and Experimental Therapeutics, Penn State College of Medicine, 500 University Drive, Hershey, PA, 17033, USA.
Scott C BunceDepartment of Psychiatry and Behavioral Health, Penn State College of Medicine, Hershey, PA, USA.
Timothy R BrickDepartment of Human Development and Family Studies, Pennsylvania State University, University Park, PA, USA.
Jennifer E NylandDepartment of Neuroscience and Experimental Therapeutics, Penn State College of Medicine, 500 University Drive, Hershey, PA, 17033, USA. jnyland@pennstatehealth.psu.edu.

Funding

Penn State Clinical and Translational Science InstituteUL1TR002014 · NCATS · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI KRASCHNEWSKI, JENNIFER L. · 2016 to 2025
$33.7M
Use of a GLP-1 Agonist to Treat Opioid Use Disorder in Rats and ManUH3DA050325 · NIDA · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI TIMOTHY R. BRICK, SCOTT C BUNCE · 2024 to 2026
$12.6M
NCATS NIH HHS UL1 TR002014NIDA NIH HHS UH3 DA050325
6 · The paper itself

Abstract

backgroundStandard 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.

methodThis 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 registrationClinicalTrials.gov: NCT06548490. Registered 12 August 2024, https://clinicaltrials.gov/study/NCT06548490 .

Indexed as

Glucagon-Like Peptide-1 Receptor AgonistsGlucagon-Like PeptidesOpioid-Related DisordersAdultAnalgesics, OpioidClinical Trials, Phase II as TopicCravingDouble-Blind MethodFemaleGlucagon-Like Peptide 1HumansMaleMulticenter Studies as TopicOutpatientsRandomized Controlled Trials as TopicSemaglutideAnalgesics, OpioidGlucagon-Like Peptide 1Glucagon-Like Peptide-1 Receptor AgonistsGlucagon-Like PeptidesSemaglutideCravingEcological momentary assessment (EMA)GLP-1RAGlucagon-like peptide-1 receptor agonistOpioid use disorder (OUD)SemaglutideSubstance use disorder (SUD)

Identifiers

PMID41168808
PMCPMC12573902

What Socratic holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.