Combination Therapy for Alcohol Use Disorder

Inclusion Criteria: * Aged 21-65 years old * Enrolled at Ashley Addiction Treatment center at least one week prior to beginning study participation. * Meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) criteria for Alcohol Use Disorder * Willing to comply with the study protocol Exclusion Criteria: * Score 9 or greater on the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) at randomization * Currently pregnant, breastfeeding * Unwilling to use contraceptives (e.g., condoms and/or hormonal birth control) * Meet criteria for another substance use disorder other than AUD, Tobacco Use Disorder, or Caffeine use disorder * History of pancreatitis * History or current diagnosis of gallbladder disease, hepatic disease, renal disease, hyperparathyroidism, or any physical health condition that would be contraindicated with GLP-1 agonists or naltrexone. * Unmanaged diabetes diagnosis or history or current diagnosis of diabetic retinopathy * Levels of amylase, lipase, aspartate aminotransferase (AST), and/or alanine transferase (ALT) greater than 2x upper limit of normal * Personal or family history of medullary thyroid carcinoma given FDA box warning for semaglutide * Diagnosis of cancer within past 5 years * History of multiple endocrine neoplasia syndrome type 2 (MEN2) * Currently taking any medications contraindicated with GLP-1 agonists and/or naltrexone. * BMI \<18.5 * Current elevated suicide risk as assessed by clinic staff or the Columbia Suicide Severity Rating Scale (C-SSRS) * Any other medical or psychological condition that is judged by the investigators to impede ability to safely complete study requirements. * Legal problems or living situation judged by the investigators as a factor that could interfere with study completion (e.g., impending jail time). * Allergies to semaglutide and/or naltrexone * Use of opioids within the past 10 days as indicated by self-report or a positive urine drug screen * Prescribed or taking the following medications in the past four weeks: * The following medications will be prohibited during study participation due to interactions with semaglutide: other GLP-1 agonists (e.g. Exenatide, liraglutide, dulaglutide), insulin, insulin-secreting medications (e.g. sulfonylureas, meglitinides), tirzepetide, dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. sitagliptin, saxagliptin, linagliptin, alogliptin, evogliptin, and gemigliptin). * The following medications will be prohibited during study participation due to interactions with naltrexone: bremelanotide, peripherally-acting mu-opioid receptor antagonists (e.g. methylnaltrexone, naldemedine), and opioid agonist medications.