Protocol published for semaglutide trial in opioid use disorder
A 200-person semaglutide trial in opioid use disorder is now on paper, but there is still no evidence that GLP-1 drugs help patients stop opioids.
Researchers published the design of a randomized, double-blind, placebo-controlled trial testing whether semaglutide, a GLP-1 receptor agonist, helps outpatients with opioid use disorder (OUD) achieve abstinence from illicit and nonprescribed opioids [1]. The protocol appeared October 30, 2025 in the journal Addiction Science & Clinical Practice [1].
The trial is planned for 200 participants enrolled in an outpatient medications-for-opioid-use-disorder (MOUD) program: 100 receiving buprenorphine and 100 receiving methadone [1]. Everyone enrolled will be someone who keeps using nonprescribed opioids despite being on one of those treatments [1].
Outcomes include the probability that a participant is abstinent from illicit and nonprescribed opioids, measures of opioid craving, and days of drug use [1]. Those measures will be collected through urine toxicology screens and self-report assessments across 19 weeks: a screening visit in Study Week 1, 12 treatment visits across Study Weeks 2 through 13, a washout visit in Study Week 14, and a final follow-up visit in Study Week 19 [1].
The protocol frames this as a phase II study. The authors write that completing it will support the feasibility of phase III trials in larger outpatient OUD populations, which "may lead to a new indication for GLP-1RA as a novel and effective treatment for OUD" [1].
The gap the trial is meant to address
In the United States, pharmacological treatment for OUD is limited to three medications: buprenorphine, methadone, and naltrexone [1]. The protocol notes that these medications work better than no treatment or behavioral therapy alone, but that patients still experience high rates of attrition and relapse [1]. People who continue using nonprescribed opioids while on MOUD face a higher risk of overdose and other health and social harms, and the protocol states that few treatment options remain for them [1]. Slow-release oral morphine and injectable opioid agonist treatment are used in some Canadian provinces and several European countries, but the protocol notes these are prohibited by the Controlled Substances Act in the United States [1].
Earlier research on GLP-1 receptor agonists in other substance use disorders is mixed. Observational studies suggest GLP-1 receptor agonists reduce craving in a residential OUD population, but the protocol states that no controlled clinical trials have been conducted to determine whether these drugs increase opioid abstinence or reduce craving in outpatients with OUD [1]. In alcohol use disorder, a placebo-controlled trial of exenatide showed reduced brain cue reactivity to alcohol on functional MRI, but heavy drinking days and total alcohol intake did not differ significantly from placebo except in a subgroup with class I obesity or greater [1]. A separate randomized trial of semaglutide in adults with alcohol use disorder found a reduction in alcohol consumed during a laboratory self-administration task, fewer drinks per drinking day, and reduced alcohol craving [1].
Why it matters for patients
Semaglutide is approved by the Food and Drug Administration for type 2 diabetes and for obesity, not for opioid use disorder [1]. This publication is a study design, not a result, so there is still no evidence from a controlled trial that semaglutide helps anyone stop using opioids, and no one can say from this document whether it will [1].
For patients already taking semaglutide under the brand names Ozempic, Wegovy, or Rybelsus, and for patients on buprenorphine or methadone, the trial is also meant to answer whether the drugs can be combined: the study enrolls people already on methadone or buprenorphine and adds semaglutide or placebo on top [1]. The protocol does not report a dosing schedule for semaglutide, how side effects will be compared between groups, or whether participants will be told which MOUD they receive alongside study drug [1]. Those details have not been disclosed in the published protocol.
What happens next
The trial is registered on ClinicalTrials.gov as NCT06548490, registered August 12, 2024 [1]. The publication date of the protocol is October 30, 2025 [1]. A start date for enrollment and a date for reporting results have not been reported [1]. The stated next step after this phase II study is a larger phase III trial, which would depend on whether this one is completed successfully [1].
Sources
Semaglutides.org provides information only, not medical advice. Talk to a licensed provider about your own care before making changes. Some telehealth links are affiliate links and are labeled where they appear.