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

A screening visit will be conducted at which written informed consent will be obtained and inclusion/exclusion criteria will be assessed. Subsequently, eligible participants will be randomly assigned to take oral semaglutide or matched placebo for 8 weeks, with the semaglutide dose titrated from 3 milligrams (mg)/day for the first 4 weeks to 7 milligrams (mg)/day for the second 4 weeks. Participants will complete 7 additional clinic visits (weekly during the first 4 weeks of the treatment period and biweekly during the second 4 weeks). At each visit, participants will also engage in a computerized behavioral intervention. At screening and again at the Week 6 visit, participants will complete an alcohol cue reactivity task. At the Week 1 visit, before ingesting the first dose of study medication, and again at the Week 8 visit, participants will complete a functional MRI session.

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.