Semaglutide Therapy for Alcohol Reduction (STAR)

Study Description: This study will test the safety/tolerability and early efficacy of subcutaneous (s.c.) semaglutide at the dose of 2.4 mg/week or maximum tolerated dose (MTD) as a potential new treatment for alcohol use disorder (AUD). Objectives: We propose to test early efficacy and safety/tolerability of semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, as a novel pharmacotherapy to reduce alcohol use and related measures. This will be a Phase 2a, pilot, proof-of-concept, outpatient study combined with experimental medicine human laboratory procedures. Endpoints: The primary aims will be to determine whether semaglutide reduces alcohol drinking from baseline to endpoint, as measured by total number of standard alcohol-containing drinks consumed per week (drinks per week, DPW). Semaglutide is safe and tolerable in individuals with AUD, as measured by the frequency/severity of adverse events and the proportion of participants who reach maximum dose, and B) semaglutide reduces alcohol drinking from baseline to endpoint, as measured by total number of standard alcohol-containing drinks consumed per week (drinks per week, DPW). The following secondary aims will also be examined: * Whether semaglutide is safe and tolerable, as assessed by the number and severity of adverse events and the proportion of participants who reach the target dose. * Whether semaglutide reduces other self-reported alcohol-related outcomes (e.g., heavy drinking days, drinks per drinking days, World Health Organization (WHO) drinking levels) * Whether semaglutide reduces blood Phosphatidylethanol (PEth) levels as a biomarker of alcohol use * Whether semaglutide reduces alcohol and/or food cue-elicited craving assessed in a bar-like laboratory * Whether semaglutide reduces and/or changes food choices in a virtual reality buffet-like laboratory