Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial.

Hendershot CS, Bremmer MP, Paladino MB, Kostantinis G, Gilmore TA, Sullivan NR, Tow AC, Dermody SS, Prince MA, Jordan R, McKee SA, Fletcher PJ, Claus ED, Klein KR

JAMA psychiatry1 Apr 2025Cited by 213 (Europe PMC)

PMID39937469PMCIDPMC11822619DOI10.1001/jamapsychiatry.2024.4789PepBankPUB-39937469

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Summary

ImportancePreclinical, observational, and pharmacoepidemiology evidence indicates that glucagon-like peptide 1 receptor agonists (GLP-1RAs) may reduce alcohol intake. Randomized trials are needed to determine the clinical significance of these findings.ObjectiveTo evaluate the effects of once-weekly subcutaneous semaglutide on alcohol consumption and craving in adults with alcohol use disorder (AUD).Design, setting, and participantsThis was a phase 2, double-blind, randomized, parallel-arm trial involving 9 weeks of outpatient treatment. Enrollment occurred at an academic medical center in the US from September 2022 to February 2024. Of 504 potential participants assessed, 48 non-treatment-seeking participants with AUD were randomized.InterventionParticipants received semaglutide (0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, and 1.0 mg for 1 week) or placebo at weekly clinic visits.Main outcomes and measuresThe primary outcome was laboratory alcohol self-administration, measured at pretreatment and posttreatment (0.5 mg/week). Secondary and exploratory outcomes, including prospective changes in alcohol consumption and craving, were assessed at outpatient visits.ResultsForty-eight participants (34 [71%] female; mean [SD] age, 39.9 [10.6] years) were randomized. Low-dose semaglutide reduced the amount of alcohol consumed during a posttreatment laboratory self-administration task, with evidence of medium to large effect sizes for grams of alcohol consumed (β, -0.48; 95% CI, -0.85 to -0.11; P = .01) and peak breath alcohol concentration (β, -0.46; 95% CI, -0.87 to -0.06; P = .03). Semaglutide treatment did not affect average drinks per calendar day or number of drinking days, but significantly reduced drinks per drinking day (β, -0.41; 95% CI, -0.73 to -0.09; P = .04) and weekly alcohol craving (β, -0.39; 95% CI, -0.73 to -0.06; P = .01), also predicting greater reductions in heavy drinking over time relative to placebo (β, 0.84; 95% CI, 0.71 to 0.99; P = .04). A significant treatment-by-time interaction indicated that semaglutide treatment predicted greater relative reductions in cigarettes per day in a subsample of individuals with current cigarette use (β, -0.10; 95% CI, -0.16 to -0.03; P = .005).Conclusions and relevanceThese findings provide initial prospective evidence that low-dose semaglutide can reduce craving and some drinking outcomes, justifying larger clinical trials to evaluate GLP-1RAs for alcohol use disorder.Trial registrationClinicalTrials.gov Identifier: NCT05520775.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

8 results from studies that gave the peptide. 8 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with alcohol use disorder, semaglutide reduced grams of alcohol consumed in a posttreatment laboratory task versus placebo.
In plain wordsIn adults with alcohol use disorder, semaglutide reduced alcohol drunk in a lab test compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseAlcohol consumed in laboratory self-administration task
Study
n = 48
Comparator
Placebo
Analysis
Primary
Outcome group
Addiction, withdrawal and alcohol intake · Mental health and mood
Studied dose
0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, 1.0 mg for 1 week · subcutaneous · 9 weeksAs given in this study (human).
Measurements
beta
−0.48
grams of alcohol consumed
Source sentences
Summary
Low-dose semaglutide reduced the amount of alcohol consumed during a posttreatment laboratory self-administration task, with evidence of medium to large effect sizes for grams of alcohol consumed (β, -0.48; 95% CI, -0.85 to -0.11; P = .01) and peak breath alcohol concentration (β, -0.46; 95% CI, -0.87 to -0.06; P = .03).
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase 2, double-blind, randomized, parallel-arm trial involving 9 weeks of outpatient treatment.
Summary · context
Of 504 potential participants assessed, 48 non-treatment-seeking participants with AUD were randomized.
Show in the study text Report a problemFND-3993746901
02HumanRandomized controlled trialEfficacy outcome
In adults with alcohol use disorder, semaglutide reduced peak breath alcohol concentration in a posttreatment laboratory task versus placebo.
In plain wordsIn adults with alcohol use disorder, semaglutide lowered peak breath alcohol in a lab test compared with placebo.
Peptide
Semaglutide
Outcome
DecreasePeak breath alcohol concentration in laboratory task
Study
n = 48
Comparator
Placebo
Analysis
Primary
Outcome group
Addiction, withdrawal and alcohol intake · Mental health and mood
Studied dose
0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, 1.0 mg for 1 week · subcutaneous · 9 weeksAs given in this study (human).
Measurements
beta
−0.46
peak breath alcohol concentration
Source sentences
Summary
Low-dose semaglutide reduced the amount of alcohol consumed during a posttreatment laboratory self-administration task, with evidence of medium to large effect sizes for grams of alcohol consumed (β, -0.48; 95% CI, -0.85 to -0.11; P = .01) and peak breath alcohol concentration (β, -0.46; 95% CI, -0.87 to -0.06; P = .03).
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase 2, double-blind, randomized, parallel-arm trial involving 9 weeks of outpatient treatment.
Summary · context
Of 504 potential participants assessed, 48 non-treatment-seeking participants with AUD were randomized.
Show in the study text Report a problemFND-3993746902
03HumanRandomized controlled trialEfficacy outcome
In adults with alcohol use disorder, semaglutide did not change average drinks per calendar day versus placebo.
In plain wordsIn adults with alcohol use disorder, semaglutide did not change average drinks per day compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeAverage drinks per calendar day
Study
n = 48
Comparator
Placebo
Outcome group
Addiction, withdrawal and alcohol intake · Mental health and mood
Studied dose
0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, 1.0 mg for 1 week · subcutaneous · 9 weeksAs given in this study (human).
Source sentences
Summary
Semaglutide treatment did not affect average drinks per calendar day or number of drinking days
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase 2, double-blind, randomized, parallel-arm trial involving 9 weeks of outpatient treatment.
Summary · context
Of 504 potential participants assessed, 48 non-treatment-seeking participants with AUD were randomized.
Show in the study text Report a problemFND-3993746903
04HumanRandomized controlled trialEfficacy outcome
In adults with alcohol use disorder, semaglutide did not change the number of drinking days versus placebo.
In plain wordsIn adults with alcohol use disorder, semaglutide did not change the number of drinking days compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeNumber of drinking days
Study
n = 48
Comparator
Placebo
Outcome group
Addiction, withdrawal and alcohol intake · Mental health and mood
Studied dose
0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, 1.0 mg for 1 week · subcutaneous · 9 weeksAs given in this study (human).
Source sentences
Summary
Semaglutide treatment did not affect average drinks per calendar day or number of drinking days
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase 2, double-blind, randomized, parallel-arm trial involving 9 weeks of outpatient treatment.
Summary · context
Of 504 potential participants assessed, 48 non-treatment-seeking participants with AUD were randomized.
Show in the study text Report a problemFND-3993746904
05HumanRandomized controlled trialEfficacy outcome
In adults with alcohol use disorder, semaglutide reduced drinks per drinking day versus placebo.
In plain wordsIn adults with alcohol use disorder, semaglutide reduced the number of drinks on drinking days compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseDrinks per drinking day
Study
n = 48
Comparator
Placebo
Outcome group
Addiction, withdrawal and alcohol intake · Mental health and mood
Studied dose
0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, 1.0 mg for 1 week · subcutaneous · 9 weeksAs given in this study (human).
Measurements
beta
−0.41
drinks per drinking day
Source sentences
Summary
but significantly reduced drinks per drinking day (β, -0.41; 95% CI, -0.73 to -0.09; P = .04)
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase 2, double-blind, randomized, parallel-arm trial involving 9 weeks of outpatient treatment.
Summary · context
Of 504 potential participants assessed, 48 non-treatment-seeking participants with AUD were randomized.
Show in the study text Report a problemFND-3993746905
06HumanRandomized controlled trialEfficacy outcome
In adults with alcohol use disorder, semaglutide reduced weekly alcohol craving versus placebo.
In plain wordsIn adults with alcohol use disorder, semaglutide reduced weekly alcohol craving compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseWeekly alcohol craving
Study
n = 48
Comparator
Placebo
Outcome group
Addiction, withdrawal and alcohol intake · Mental health and mood
Studied dose
0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, 1.0 mg for 1 week · subcutaneous · 9 weeksAs given in this study (human).
Measurements
beta
−0.39
weekly alcohol craving
Source sentences
Summary
weekly alcohol craving (β, -0.39; 95% CI, -0.73 to -0.06; P = .01)
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase 2, double-blind, randomized, parallel-arm trial involving 9 weeks of outpatient treatment.
Summary · context
Of 504 potential participants assessed, 48 non-treatment-seeking participants with AUD were randomized.
Show in the study text Report a problemFND-3993746906
07HumanRandomized controlled trialEfficacy outcome
In adults with alcohol use disorder, semaglutide predicted greater reductions in heavy drinking over time relative to placebo.
In plain wordsIn adults with alcohol use disorder, semaglutide was linked to bigger drops in heavy drinking over time than placebo.
Peptide
Semaglutide
Outcome
DecreaseHeavy drinking over time
Study
n = 48
Comparator
Placebo
Outcome group
Addiction, withdrawal and alcohol intake · Mental health and mood
Studied dose
0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, 1.0 mg for 1 week · subcutaneous · 9 weeksAs given in this study (human).
Measurements
beta
0.84
heavy drinking over time
Source sentences
Summary
also predicting greater reductions in heavy drinking over time relative to placebo (β, 0.84; 95% CI, 0.71 to 0.99; P = .04)
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase 2, double-blind, randomized, parallel-arm trial involving 9 weeks of outpatient treatment.
Summary · context
Of 504 potential participants assessed, 48 non-treatment-seeking participants with AUD were randomized.
Show in the study text Report a problemFND-3993746907
08HumanRandomized controlled trialEfficacy outcome
In adults with alcohol use disorder and current cigarette use, semaglutide predicted greater relative reductions in cigarettes per day over time versus placebo.
In plain wordsIn adults with alcohol use disorder who smoked, semaglutide was linked to bigger drops in cigarettes per day than placebo.
Peptide
Semaglutide
Outcome
DecreaseCigarettes per day in current cigarette users
Study
n: not reported in source
Comparator
Placebo
Outcome group
Addiction, withdrawal and alcohol intake · Mental health and mood
Studied dose
0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, 1.0 mg for 1 week · subcutaneous · 9 weeksAs given in this study (human).
Measurements
beta
−0.1
cigarettes per day
Source sentences
Summary
A significant treatment-by-time interaction indicated that semaglutide treatment predicted greater relative reductions in cigarettes per day in a subsample of individuals with current cigarette use (β, -0.10; 95% CI, -0.16 to -0.03; P = .005).
2 context sentences(design, population, supporting numbers)
Summary · context
This was a phase 2, double-blind, randomized, parallel-arm trial involving 9 weeks of outpatient treatment.
Summary · context
Of 504 potential participants assessed, 48 non-treatment-seeking participants with AUD were randomized.
Show in the study text Report a problemFND-3993746908

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials2

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

2 trials · 1 ongoing · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

Active, not recruitingPhase 1NCT07223983

Semaglutide (SEMA) for Alcohol Use Disorder (AUD) After Metabolic and Bariatric Surgery (MBS)

Yale Universityn = 426 Mar 2026 to est. Feb 2027

Alcohol Use Disorder · Weight Loss · Bariatric Surgery Patients

Trial page ClinicalTrials.govUpdated 10 Sept 2026

CompletedPhase 2Results postedNCT05520775

Semaglutide for Alcohol Use Disorder

University of North Carolina, Chapel Hilln = 482 Sept 2022 to 19 Apr 2024

Alcohol Use Disorder · Cigarette Smoking

Trial page ClinicalTrials.govUpdated 2 Apr 2025

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
11 Oct 2026, 00:04 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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