NCT05520775

Semaglutide for Alcohol Use Disorder

Completed Phase 2 Results posted Last updated 2 April 2025

What this trial tests

Phase 2 trial testing Semaglutide in Alcohol Use Disorder in 48 participants. Completed in 19 April 2024.

Timeline

2 September 2022

Primary endpoint
12 April 2024

19 April 2024

Quick facts

Lead sponsor	University of North Carolina, Chapel Hill
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	basic science
Enrollment	48
Start date	2 September 2022
Primary completion	12 April 2024
Estimated completion	19 April 2024
Sites	1 location across United States

Drugs / interventions tested

• Semaglutide (semaglutide) — full drug profile →
• Sham/placebo — full drug profile →

Conditions studied

• Alcohol Use Disorder — all drugs for Alcohol Use Disorder →
• Cigarette Smoking — all drugs for Cigarette Smoking →

Sponsor

University of North Carolina, Chapel Hill

Who can join

Adults 21 to 65, any sex, with Alcohol Use Disorder or Cigarette Smoking. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Alcohol Consumed Primary · Baseline (Week 0) to post-medication (Week 8)

Estimated grams of ethanol consumed.

Group	Value	95% CI
Semaglutide	-32.72	± 27.98
Sham/Placebo	-6.95	± 24.49

Change in Breath Alcohol Concentration Primary · Baseline (Week 0) to post-medication (Week 8)

Peak breath alcohol concentration following an alcohol self-administration procedure.

Group	Value	95% CI
Semaglutide	-0.034	± 0.045
Sham/Placebo	-0.016	± 0.047

Change in Subjective Stimulation (Biphasic Alcohol Effects Scale) Secondary · Baseline (Week 0) to post-treatment (Week 8)

Seven questions from the Biphasic Alcohol Effects Scale used to collect self-reported feelings of stimulation during an alcohol challenge procedure. Possible responses are 0-10, 0 being "not at all" and 10 being "extremely". Scale score ranges from 0 to 70. Higher scores indicate greater stimulation effects.

Group	Value	95% CI
Semaglutide	.45	± 12.82
Sham/Placebo	-1.28	± 13.49

Change in Subjective Sedation (Biphasic Alcohol Effects Scale) Secondary · baseline (Week 0) to post-medication (Week 8)

Seven questions from the Biphasic Alcohol Effects Scale used to collect self-reported sedative effects during an alcohol challenge procedure. Possible responses are 0 "not at all" through 10 "extremely". Scale scores range from 0 to 70. Higher scores indicate greater sedative effects.

Group	Value	95% CI
Semaglutide	0.14	± 10.69
Sham/Placebo	-3.22	± 7.89

Change in Alcohol Demand (Alcohol Purchase Task) Secondary · Baseline (Week 0) to post-treatment (Week 8)

The Alcohol Purchase Task is a 20-question self-report measure which asks participants about the number of drinks they would purchase and consume based at different monetary costs. Intensity scores reflect the number of drinks that would be purchased when cost is zero.

Group	Value	95% CI
Semaglutide	-2.91	± 3.73
Sham/Placebo	-2.90	± 7.82

Change in Cigarette Demand (Cigarette Purchase Task) Secondary · Baseline (Week 0) to Post-medication (Week 8)

Self-report cigarette demand as measured by the Cigarette Purchase Task. Intensity scores reflect the number of cigarettes that would be purchased when cost is zero.

Group	Value	95% CI
Semaglutide	-2.4	± 2.61
Sham/Placebo	-1.20	± 2.17

Change in Daily Alcohol Use Secondary · baseline (Week 0) to study endpoint (Week 10)

Self-reported drinks per day averaged across study week.

Group	Value	95% CI
Semaglutide	-1.43	± 1.51
Sham/Placebo	-0.81	± 2.45

Change in Daily Cigarette Use Secondary · baseline (Week 0) to study endpoint (Week 10)

Self-reported cigarettes per day

Group	Value	95% CI
Semaglutide	-2.48	± 4.22
Sham/Placebo	-1.30	± 2.10

Adverse events — posted to ClinicalTrials.gov

Time frame: From the Baseline medical visit through follow-up, a total of up to 12 weeks.. Reporting threshold: 4%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Semaglutide

Serious: 0/24 (0%)

Deaths: 0/24

Sham/Placebo

Serious: 0/24 (0%)

Deaths: 0/24

Other adverse events (14 terms — click to expand)

Reaction	System	Semaglutide	Sham/Placebo
Decreased Appetite	Nervous system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Headache	Nervous system disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Fatigue	Nervous system disorders	—	—
Nervousness/Anxiety	Nervous system disorders	—	—
Abdominal Pain	Gastrointestinal disorders	—	—
Insomnia	Nervous system disorders	—	—
Increased Appetite	Nervous system disorders	—	—
Dizziness	Nervous system disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Depression	Psychiatric disorders	—	—
Increased Libido	General disorders	—	—

Data from ClinicalTrials.gov NCT05520775 adverse events section.

Sponsor's own description

This is an early-Phase II human laboratory trial using a randomized, placebo-controlled, dose-ranging design to investigate the effects of semaglutide, a GLP-1 receptor agonist, on alcohol-related outcomes in adults with alcohol use disorder (AUD).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial.
   Hendershot CS, Bremmer MP, Paladino MB, Kostantinis G, et al · · 2025 · cited 113× · PMID 39937469 · DOI 10.1001/jamapsychiatry.2024.4789
2. IUPHAR review - Glucagon-like peptide-1 (GLP-1) and substance use disorders: An emerging pharmacotherapeutic target.
   Bruns Vi N, Tressler EH, Vendruscolo LF, Leggio L, et al · · 2024 · cited 48× · PMID 39032839 · DOI 10.1016/j.phrs.2024.107312
3. Effect of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide on alcohol consumption in alcohol-preferring male vervet monkeys.
   Fink-Jensen A, Wörtwein G, Klausen MK, Holst JJ, et al · · 2025 · cited 36× · PMID 38884652 · DOI 10.1007/s00213-024-06637-2
4. Glucagon-like peptide-1 receptor agonists, but not dipeptidyl peptidase-4 inhibitors, reduce alcohol intake.
   Farokhnia M, Tazare J, Pince CL, Bruns N, et al · · 2025 · cited 26× · PMID 40048376 · DOI 10.1172/jci188314
5. Ecological momentary assessment and cue-elicited drug craving as primary endpoints: study protocol for a randomized, double-blind, placebo-controlled clinical trial testing the efficacy of a GLP-1 receptor agonist in opioid use disorder.
   Freet CS, Evans B, Brick TR, Deneke E, et al · · 2024 · cited 10× · PMID 39061093 · DOI 10.1186/s13722-024-00481-7
6. Semaglutide as a GLP-1 Agonist: A Breakthrough in Obesity Treatment.
   Salvador R, Moutinho CG, Sousa C, Vinha AF, et al · · 2025 · cited 9× · PMID 40143174 · DOI 10.3390/ph18030399
7. Effects of GLP-1 Receptor Agonists in Alcohol Use Disorder.
   Klausen MK, Knudsen GM, Vilsbøll T, Fink-Jensen A. · · 2025 · cited 8× · PMID 39891507 · DOI 10.1111/bcpt.70004
8. Closing the Care Gap: Management of Alcohol Use Disorder in Patients with Alcohol-associated Liver Disease.
   Green EW, Byers IS, Deutsch-Link S. · · 2023 · cited 8× · PMID 38052695 · DOI 10.1016/j.clinthera.2023.09.017