Clinical Trial of Rybelsus (Semaglutide) Among Adults With Alcohol Use Disorder (AUD)

Inclusion Criteria: Age 21 or older. Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for current AUD of at least moderate severity, as assessed by the Mini International Neuropsychiatric Interview (MINI). Seeking pharmacological treatment for AUD and wants to stop or cut down on drinking. Has a body mass index (BMI) of at least 25 kg/m2. Able to read and understand questionnaires and informed consent. Lives within 50 miles of the study site. Please contact clinical site for additional inclusion criteria. Exclusion Criteria: Current DSM-5 diagnosis of any other substance use disorder of moderate or greater severity, except for Nicotine Use Disorder, as assessed by MINI. Urine drug screen at screening positive for any substance except cannabis. Current DSM-5 bipolar disorder, major depressive episode, or panic disorder, as assessed by MINI. Current or lifetime eating disorder (anorexia, bulimia, or binge eating disorder) or psychotic disorder, as assessed by MINI. Current suicidal ideation or homicidal ideation. Current use of other psychotropic medications except antidepressants (for which dose must be stable for at least the past 2 months). Current or past-month use of AUD pharmacotherapy, including (e.g., oral naltrexone, acamprosate, or disulfiram) or current or past 60-day use of injectable naltrexone. Current psychotherapy in which the primary focus is AUD. Attendance at Alcoholics Anonymous (AA) meetings is not exclusionary. Current or past-month use of weight control medications. Current or past-month use of metformin for any indication. Any prior use of semaglutide or other GLP-1 agonists. History of severe alcohol withdrawal (e.g., seizure, delirium tremens), as evidenced by self- report and assessment with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar). Current or lifetime Type 1 or Type 2 diabetes diagnosis, or HbA1c >6.5%. Current or lifetime kidney disease or creatinine clearance <80 mL/min for participants <=55 years of age (<65 mL/min for those >55). Personal history of gastrointestinal disease (e.g., gastroparesis) or pancreatitis. Personal or family history of medullary thyroid carcinoma and/or multiple endocrine neoplasia syndrome type 2 Current or past hepatocellular disease, as indicated by verbal report or elevations of serum amylase, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of the normal range at screening. Uncontrolled hypertension (systolic BP >160 mmHg or diastolic >100 mmHg). Biological females of childbearing potential who are pregnant (by plasma HCG), nursing, or who are not using a reliable form of contraception. Lack of a stable living situation. (If participating in MRI sessions) Contraindications to MRI scanning, ferrous metal in the body including intracranial, intraorbital, or intraspinal metal, pacemakers, cochlear implants, other non-MRI-compatible devices, or other devices that could compromise the quality of the MRI images such as a permanent top retainer or braces. (If participating in MRI sessions) Severe claustrophobia or morbid obesity that preclude placement in the MRI scanner.