Clinical Trial of Rybelsus (semaglutide) Among Adults with Alcohol Use Disorder (AUD)

Eligibility Criteria

• 1. Age 21 or older.
• 2. 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).
• 3. Seeking pharmacological treatment for AUD and wants to stop or cut down on drinking.
• 4. Has a body mass index (BMI) of at least 25 kg/m2.
• 5. Able to read and understand questionnaires and informed consent.
• 6. Lives within 50 miles of the study site.
• 1. Current DSM-5 diagnosis of any other substance use disorder of moderate or greater severity, except for Nicotine Use Disorder, as assessed by MINI.
• 2. Urine drug screen at screening positive for any substance except cannabis.
• 3. Current DSM-5 bipolar disorder, major depressive episode, or panic disorder, as assessed by MINI.
• 4. Current or lifetime eating disorder (anorexia, bulimia, or binge eating disorder) or psychotic disorder, as assessed by MINI.
• 5. Current suicidal ideation or homicidal ideation.
• 6. Current use of other psychotropic medications except antidepressants (for which dose must be stable for at least the past 2 months).
• 7. 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.
• 8. Current psychotherapy in which the primary focus is AUD. Attendance at Alcoholics Anonymous (AA) meetings is not exclusionary.
• 9. Current or past-month use of weight control medications.
• 10. Current or past-month use of metformin for any indication.
• 11. Any prior use of semaglutide or other GLP-1 agonists.
• 12. 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).
• 13. Current or lifetime Type 1 or Type 2 diabetes diagnosis, or HbA1c \>6.5%.
• 14. Current or lifetime kidney disease or creatinine clearance \<80 mL/min for participants \<=55 years of age (\<65 mL/min for those \>55).
• 15. Personal history of gastrointestinal disease (e.g., gastroparesis) or pancreatitis.
• 16. Personal or family history of medullary thyroid carcinoma and/or multiple endocrine neoplasia syndrome type 2
• 17. 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.
• 18. Uncontrolled hypertension (systolic BP \>160 mmHg or diastolic \>100 mmHg).
• 19. Biological females of childbearing potential who are pregnant (by plasma HCG), nursing, or who are not using a reliable form of contraception.
• 20. Lack of a stable living situation.
• 21. (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.
• 22. (If participating in MRI sessions) Severe claustrophobia or morbid obesity that preclude placement in the MRI scanner.