Cessation or Reduction of Alcohol Consumption in Veterans: A Randomized Controlled Trial for Alcohol Use Disorder (CRAVE)

Inclusion Criteria: * Veteran * World Health Organization's (WHO) risk drinking level of Very High or High in the 28 days prior to screening (based on screening TLFB) * Current diagnosis of moderate or severe alcohol use disorder (AUD), i.e., meeting at least 4 of 11 DSM-5 AUD criteria, based on semi-structured diagnostic exam, the Mini-International Neuropsychiatric Interview (MINI) * Able and willing to provide informed consent * Has a desire to reduce their alcohol consumption Exclusion Criteria: * Medical History (medical history form) * Type 1 diabetes * History of acute or chronic pancreatitis * History of diabetic ketoacidosis * History of proliferative diabetic retinopathy * History of ascites, advanced liver fibrosis, compensated cirrhosis with portal hypertension, decompensated cirrhosis, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or hepatocellular carcinoma (HCC) * History of advanced fibrosis or cirrhosis, including (but not limited to) transient elastography (liver stiffness) of \>12 kPa, FIB-4 ≥2.67, ELF ≥9.8, MRE ≥3.63 kPa * History of stage 3 fibrosis or stage 4 cirrhosis from a liver biopsy * History of esophageal varices on endoscopy or imaging * History of nodular liver, cirrhosis, splenomegaly, varices or splenic venous shunting or collaterals on prior imaging * History or acute alcohol hepatitis (by liver biopsy or elevated bilirubin \> 1.5 times the upper limit of normal) * History of primary biliary cholangitis * History of primary sclerosing cholangitis * Current drug-induced liver disease * History of alpha1 antitrypsin deficiency related liver disease * History of autoimmune liver disease * History of hemochromatosis * History of Wilson's disease * Presence of gastroparesis * History of acute gallbladder disease in the prior 6 months * Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2) * Unstable body weight defined as \>5% change in body weight (documented or self-report; intentional or not) in the 90 days prior to randomization * Recent major cardiovascular event in the 90 days prior to randomization (myocardial infarction, stroke, New York Heart Association class IV heart failure, transient ischemic attack (TIA), or unstable angina * Known history of prior hypersensitivity reaction to semaglutide, any of the product components, or any other GLP-1 analogue * Concurrent Treatments (medical history form): * Current (within the past 30 days) use of pharmacotherapy for alcohol use disorder (AUD), including oral or intramuscular naltrexone, acamprosate, disulfiram, topiramate * Current (within the past 30 days) use of the following medications with glucose-lowering properties: GLP-1 analogues; sulfonylurea; insulin and insulin products; dipeptidyl peptidase-4 (DPP-4) inhibitors; sodium-glucose cotransporter-2 (SGLT-2) inhibitors, meglitinides, thiazolidinediones or other medications that may interact with semaglutide * Recent changes in dose (within 2 months of randomization) of psychiatric medications (i.e., antidepressants, antianxiety, mood stabilizing) * Psychiatric diagnosis, the Mini-International Neuropsychiatric Interview (MINI) * Current serious psychiatric illness (any psychotic disorder, bipolar 1 disorder, psychotic major depression, antisocial personality disorder, bulimia, or anorexia) * Current DSM-5 diagnosis of a Substance use disorder (SUD), other than moderate-to-severe alcohol, any nicotine, or mild cannabis use disorders * Other assessments (local site) * At the time of randomization, moderate-to-severe alcohol withdrawal (Clinical Institute Withdrawal Assessment for Alcohol (CIWA-AR) \>8) * Body mass index (BMI) \<21 kilograms/square meter (kg/m2) * Acute high risk of suicide requiring hospitalization at the time of screening or randomization * Medical, psychiatric, behavioral, or logistical conditions which, in the judgment of the Local Site Investigator (LSI) or Co-Investigator (Co-I), make it unlikely the participant can participate in or complete the 24-week active phase of the study * Pregnant, actively breastfeeding, or female of childbearing potential who is unwilling to use a highly effective method of contraception as defined by the NIH * Currently enrolled in another therapeutic or investigational clinical trial without a preexisting dual enrollment agreement * Participant is incarcerated * Laboratory * Hemoglobin A1c (HbA1c)\>10 * Estimated glomerular filtration rate (eGFR) \<30 milliliters/minute (mL/min) * Albumin \< 3.5 grams/deciliter (g/dl) * Aspartate aminotransferase (AST) \>3 the Upper Limit of Normal (ULN) * Alanine aminotransferase (ALT) \>3 the ULN * Lipase \> 2 times the upper limit of normal * Alkaline phosphatase \> 1.5 times the ULN * Total bilirubin \> 1.5 times the ULN except with documented Gilbert's syndrome * International Normalized Ratio (INR) \> 1.3 unless due to anticoagulation therapy * Platelet count \<150,000/ liter (L) unless consistent with baseline and reflects the participant's habitual thrombocyte level, and there was no presence of portal hypertension * Hepatitis B surface antigen positive * Hepatitis C virus RNA positive - participants treated and cured of hepatitis C must have at least 2 years of negative testing * Anti-HIV antibody positive test with uncontrolled or unstable treatment * Positive urine drug screen for substances other than cannabis and prescribed medications * Positive urine pregnancy test at screening in those considered of childbearing potential