Semaglutide Therapy for Alcohol Reduction - Tulsa (STAR-T)

Inclusion Criteria: Ability to provide informed consent before any trial-related activities Male or female individuals who are at least 18 years old Alcohol Use Disorder (minimum 2 symptoms on a validated diagnostic tool, e.g., DSM-5 Checklist for Alcohol Use Disorder, the Mini-International Neuropsychiatric Interview (MINI) or the Structured Clinical Interview for DSM Disorders (SCID)) Self-reported drinking, according to alcohol TimeLine Follow-Back (TLFB), of > 7 drinks per week for females or > 14 drinks per week for males during the 28-day period prior to screening + at least four days with > 3 drinks for females or > 4 drinks for males during the 28-day period prior to screening. Most recent Clinical Institute Withdrawal Assessment for Alcohol - revised (CIWA-Ar) score is ≤ 10 Able to speak, read, write, and understand English Normal or corrected-to-normal (e.g., wearing glasses or contacts) vision and normal or corrected-to-normal (e.g., with the use of a hearing aid) hearing Female participants must be postmenopausal for at least one year, surgically sterile, or practicing a highly effective method of birth control before entry and throughout the study and must have a negative urine pregnancy test at each visit. Examples of birth control methods include (but are not limited to) oral contraceptives or contraceptive implants, barrier methods such as diaphragms with contraceptive jelly, cervical caps with contraceptive jelly, condoms, intrauterine devices, a partner with a vasectomy, or abstinence from intercourse. Exclusion Criteria: BMI < 25 kg/m2 or BMI ≥ 50 kg/m2 Evidence of malnutrition as determined by the Nutrition Risk Screening 2002 (NRS-2002) Most recent blood tests: creatinine ≥ 2 mg/dL, eGFR ≤ 60 mL/min/1.73 m2, triglycerides > 500 mg/dl, ALP > 4x the upper normal limit, abnormal blood lipase levels Present diagnosis of diabetes or blood hemoglobin A1c (HbA1c) ≥ 6.5 % Current use of the following medications with glucose lowering properties: GLP-1 analogues, sulfonylurea, insulin, metformin, thiazolidinediones (TZD), dipeptidyl peptidase-4 (DPP-IV) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors Current or prior use of semaglutide (Ozempic or Wegovy) or tirzepatide (Mounjaro). Use of weight-lowering/anti-obesity medications within the past 90 days prior to enrollment in the study. Current use of FDA-approved pharmacotherapy for AUD (acamprosate, disulfiram, naltrexone), or other medications that are used for AUD treatment including topiramate and bupropion. Due to the half-life of injectable naltrexone, we will exclude participants who have taken vivitrol in the past 30 days. Current use of medications with known interactions with semaglutide Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) Known history of alcoholic ketoacidosis, pancreatitis (either acute or chronic), pancreatic carcinoma, gallbladder disease, jaundice, Mallory-Weiss syndrome (esophageal tears secondary to vomiting), esophageal varices, cirrhosis Known history of gastric bypass surgery Known or suspected allergy to semaglutide, any of the product components, or any other GLP-1 analogue Known history of suicidal attempts (within the past 24 months) or active suicidal ideation Known history of vestibular disorders or clinically significant motion sickness Known history of noise-induced hearing loss or tinnitus Only for subjects undergoing brain scan: contraindication(s) for brain fMRI Unstable cardiovascular conditions (e.g., arrhythmias, clinically significant ECG abnormalities) Physical and/or mental health conditions that are clinically unstable, as determined by the study clinicians, including (but not limited to) major depressive disorder or generalized anxiety disorder unstable within the past three months or other psychiatric conditions (e.g., schizophrenia, bipolar disorder) unstable within the past twelve months. Current stimulant or opioid use disorder. Any other reason or clinical condition that the Investigators judge would interfere with study participation and/or be unsafe for a possible subject