Semaglutide to support recovery from opioid use disorder

Semaglutide for the Treatment of Opioid Use Disorder: A Pilot Randomized Controlled Trial

Phase 2 Interventional Brigham and Women's Hospital · NCT06639464

This 12-week test tries weekly semaglutide injections in people with opioid use disorder who recently started buprenorphine to see if it reduces cue-reactivity and improves symptoms and safety measures.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment46 (estimated)
Ages18 Years and up
SexAll
SponsorBrigham and Women's Hospital Academic / other
Locations1 site (Boston, Massachusetts)
Trial IDNCT06639464 on ClinicalTrials.gov

What this trial studies

This is a double-blind, placebo-controlled, randomized pilot enrolling 46 adults with DSM-5 opioid use disorder who have been on a stable sublingual buprenorphine dose for at least 30 days. Participants are randomized 1:1 to weekly semaglutide injections or matching placebo for 12 weeks with 13 scheduled visits that include neurocognitive testing for reward- and stress-related cue-reactivity, vitals, urine toxicology, and blood draws. The trial collects safety and tolerability data, measures of craving and withdrawal, mood symptoms, and blood biomarkers at baseline, mid-treatment, and end of study. Both participants and study staff are blinded to treatment assignment to limit bias.

Who should consider this trial

Good fit: Adults (18+) with severe DSM-5 opioid use disorder who initiated sublingual buprenorphine within 60 days, have been on a stable buprenorphine dose of 16 mg or greater for at least 30 days, and are willing to attend weekly visits and allow communication with their buprenorphine prescriber.

Not a fit: People with current substance use disorders other than opioid/cannabis/tobacco, active psychosis or suicidality, any current or past eating disorder, BMI under 25, or uncontrolled diabetes are excluded and therefore unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, semaglutide could reduce cue-driven craving and improve treatment outcomes for people starting buprenorphine for opioid use disorder.

How similar studies have performed: Preclinical work and early human studies of GLP-1 receptor agonists suggest potential to reduce drug-related cue-reactivity, but using semaglutide specifically for opioid use disorder is a novel, early pilot approach.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* English speaking adults aged 18 and above
* DSM-5 diagnosis of opioid use disorder, severe
* Initiated sublingual buprenorphine (SL-BUP) treatment within 60 days of enrollment
* Attained stable dosing of SL-BUP of 16mg or greater for 30 days prior to enrollment
* Anticipating continuation of SL-BUP for the duration of the trial
* Agreeable with bringing SL-BUP prescription to visits to allow study team to conduct a dose count
* Willing to grant study team permission to communicate about SL-BUP treatment with community prescriber via completion of 42 CFR release

Individuals with any of the following will be excluded:

* DSM-5 diagnosis of any current substance use disorder excluding opioid, cannabis or tobacco
* Active psychosis, active suicidality or homicidality or any psychiatric condition that impair ability to provide informed consent
* Any current or lifetime diagnosis of eating disorders
* BMI\<25mg/kg2
* Current or lifetime diagnosis of Type 1 or Type 2 diabetes
* Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
* Use of any GLP-1 agonist medications in the prior 3 months
* Anticipating receipt of any GLP-1 agonist medications during the trial
* History of angina pectoris, coronary heart disease, congestive heart failure, inflammatory bowel disease, chronic obstructive pulmonary disease, bariatric surgery, idiopathic pancreatitis, diabetic gastroparesis
* Liver function test greater than 3 times upper normal limit
* Renal impairment as indicated by eGFR of \<60
* History of hypersensitivity or allergy to semaglutide
* Pregnant or breastfeeding
* Anticipated to participate in a concurrent drug trial
* Any other reason or clinical condition that the investigators judge may interfere with study participation and/or be unsafe for a participant

Where this trial is running

Boston, Massachusetts

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Opioid Use Disordersemaglutideopioid use disorderbuprenorphine
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.