GLP-1R Agonist Treatment for Opioid Use Disorder

The goal of this clinical trial is to learn if semaglutide can reduce illicit opioid use in adults in outpatient treatment for opioid use disorder, and who are receiving either buprenorphine or methadone maintenance treatment. The main question it aims to answer is: • Does semaglutide increase the likelihood that participants will refrain from using illicit and nonprescribed opioids? The investigators will compare semaglutide to a placebo (a needle prick that contains no drug) to see if semaglutide works to reduce use of illicit and nonprescribed opioids. The participants will: * Take semaglutide or a placebo every week for 12 weeks * Visit the clinic every week for urine drug screening and pregnancy testing, vital signs, and to complete mental health and drug use questionnaires * Complete smartphone surveys sent at set times during the study

Inclusion Criteria: * 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 anatomically 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 to abstain from sexual intercourse 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 Criteria: * Age \< 18 or \> 75 years. * BMI \