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.
