GLP-1R Agonist Treatment for Opioid Use Disorder

This study is investigating whether semaglutide, a drug given by injection pen, can help reduce the use of illicit (illegal) and nonprescribed opioids in adults. You could be eligible if you are between 18 and 75 years old, have a body mass index (BMI) over 18, and have an opioid use disorder. You must also be receiving buprenorphine or methadone treatment. The study will compare semaglutide to a placebo (a dry needle stick with no medicine) to see if semaglutide increases the number of participants who are abstinent from illicit and nonprescribed opioids at weeks 2, 3, and 4 of the study. The study aims to enroll 200 participants, but its current status is unclear.

Study design: This is an interventional study comparing semaglutide to a placebo in about 200 participants. Participants will be randomly assigned to receive either semaglutide or placebo.
What's involved: You would receive weekly injections of semaglutide or placebo for 12 weeks in an outpatient setting. There will be a baseline evaluation and data collection period before treatment begins.
Compensation: Not stated in the trial record.
Follow-up: After 12 weeks of treatment, participants will discontinue the study intervention and be observed for an additional week.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

GLP-1R Agonist Treatment for Opioid Use Disorder

Recruiting

PHASE2Ages 18–75InterventionalTreatment

Milton S. Hershey Medical Center

~200 participants

Updated 2026-08-28 on ClinicalTrials.gov

What's tested:Semaglutide Pen InjectorPlacebo

At a glance

Recruiting sites

3 of 4 listed sites are recruiting right now

RecruitingSuspended, closed, or not yet open

What they're measuring

Number of participants being abstinent from illicit and nonprescribed opioids.

Measured over Study week 2

+11 more outcomes measured

Conditions

Opioid Use Disorder

Opioid Abuse and Addiction

Narcotic-Related Disorders

Substance-Related Disorders

Chemically-Induced Disorders

Mental Disorder

Opioid

Where it's being run

4 sites across 4 states

Maryland1

Massachusetts1

New York1

Pennsylvania1

Study leadership

Jennifer Nyland, PhD · PRINCIPAL_INVESTIGATOR · Milton S. Hershey Medical Center

Who to contact

Jennifer Nyland, PhD

[email protected]

717-531-6172

Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

Age 18 to 75 years.

Body mass index (BMI) \> 18.

Able and willing to provide informed consent prior to any study-related activities.

Current diagnosis of Diagnostic and Statistical Manual Diploma in Social Medicine (DSM)-5 Opioid Use Disorder (OUD) as per the Mini International Neuropsychiatric Interview (MINI) or per the site clinic diagnosis. Patients are eligible if they have a MINI \> 3 ("moderate" or "severe" in the "Specify If" box in the Substance Use Disorder (Non-Alcohol) module for the category of opiates).

Currently receiving outpatient treatment for OUD and at least 2 weeks on buprenorphine (BUP) or 4 weeks on methadone at the study site and/or at an associated clinic at the time of enrollment.

Have at least 1 urine test positive for opioids after 2 weeks on BUP or 4 weeks on methadone.

Have positive self-reporting of opioid use after 2 weeks on BUP or 4 weeks on methadone.

If capable of becoming pregnant and of childbearing age, is not pregnant (confirmed) or breastfeeding at the time of enrollment and agrees to use a medically accepted method of birth control or or to abstain from sexual activity that could result in pregnancy (if applicable) while in the study.

Able to read and communicate in English to the level required to accept standard care and complete all study requirements.

Able and willing to engage/adhere to the entirety of the study protocol (19 weeks).

Not currently a prisoner.

Exclusion

Age \< 18 or \> 75 years.

BMI \<18.

Individuals who are pregnant, planning pregnancy, breastfeeding, or unwilling to use adequate contraceptive measures.

Current use of glucagon-like peptide 1 receptor (GLP-1R) agonist.

History of angioedema, serious hypersensitivity reaction, or anaphylactic reaction to semaglutide or another GLP-1R agonist.

Personal or family history of medullary thyroid carcinoma (MTC) or patients with multiple endocrine neoplasia syndrome Type 2 (MEN 2) or thyroid nodule.

Type 1 diabetes or history of diabetic ketoacidosis.

Type 2 diabetes mellitus or current use of a dipeptidyl peptidase-4 (DPP-4) inhibitor.

Past 30-day use of Sincalide, Sulfonylureas, insulin and insulin products or other medications that may interact with semaglutide.

Hypoglycemia on intake visit (blood glucose \< 60 mg/dL).

End-stage renal failure, on dialysis, or glomerular filtration rate (GFR) \<30 mL/min per 1.73 square meters or previous renal transplant.

End stage liver disease or previous liver transplant.

Current or past diagnosis of pancreatitis, gastroparesis, or other severe gastrointestinal (GI) disease.

Current or past diagnosis of gallbladder disease or gallstones.

Serious cardiovascular disease within the past 6 months (e.g. uncontrolled hypertension, heart failure, significant cardiac arrhythmias, myocardial infarction, presence of angina pectoris, symptomatic coronary artery disease, deep vein thrombosis, pulmonary embolism, second- or third-degree heart block, mitral valve or aortic stenosis, hypertrophic cardiomyopathy, stroke).

Severe co-occurring psychiatric disorder (e.g., bipolar disorder, psychotic disorder, schizophrenia), and/or history or evidence of organic brain disease or dementia that would compromise safety or compliance with the study protocol in the opinion of the site principal investigator (PI) and/or physician. As there is no specific scale that determines this, this will include the Site PI/physician determining if the potential participant shows consistency in decision making and if they are alert and oriented to time, date, day and location.

Significant risk of suicide requiring a different/higher level of care, according to the clinical judgment of the study physician or site principal investigator, or history of suicide attempts within the past 1 year, unless participation is cleared by clinician assessment and/or judgment. A Columbia-Suicide Severity Rating Scale (C-SSRS) indicating a history of suicide attempts within the past year, or active suicidal ideation within the past 1 month, will qualify as significant risk of suicide.

Treatment with any investigational drug in the one month preceding the study.

Any contraindication to both methadone and BUP.

Any contraindication to a GLP-1R agonist.

Previous randomization for participation in this trial.

Any other condition at screening that precludes safe participation in the trial in the judgment of the site PI or study physician.

Plans for travel outside of the local area over the 19 weeks (1 week of baseline, 12 weeks of medication, 1 week wash-out, and follow-up after a further 28 days) that would interfere with visits during the study period or other logistic factors that would make it difficult to commit to the entire duration of study.

Currently a prisoner.

What this trial measures

Number of participants being abstinent from illicit and nonprescribed opioids.Study week 2
Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.
Number of participants being abstinent from illicit and nonprescribed opioids.Study week 3
Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.
Number of participants being abstinent from illicit and nonprescribed opioids.Study week 4
Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.
Number of participants being abstinent from illicit and nonprescribed opioids.Study week 5
Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.
Number of participants being abstinent from illicit and nonprescribed opioids.Study week 6
Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.
Number of participants being abstinent from illicit and nonprescribed opioids.Study week 7
Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.
Number of participants being abstinent from illicit and nonprescribed opioids.Study week 8
Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.
Number of participants being abstinent from illicit and nonprescribed opioids.Study week 9
Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.
Number of participants being abstinent from illicit and nonprescribed opioids.Study week 10
Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.
Number of participants being abstinent from illicit and nonprescribed opioids.Study week 11
Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.
Number of participants being abstinent from illicit and nonprescribed opioids.Study week 12
Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.
Number of participants being abstinent from illicit and nonprescribed opioids.Study week 13
Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.

Trialytics