Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial.

Klausen MK, Justesen SK, Pedersen JN, Rasmussen L, Jensen A, Jensen ME, Knorr UB, Bergmann ML, Holst JJ, Hartmann B, Koob GF, Benveniste H and 5 more

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Volkow ND, Ekstrøm CT, Knudsen GM, Vilsbøll T, Fink-Jensen A

Lancet (London, England)1 May 2026Cited by 20 (Europe PMC)

PMID42070571DOI10.1016/s0140-6736(26)00305-3PepBankPUB-42070571

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Summary

BackgroundAlcohol use disorder accounts for 5% of deaths worldwide annually, and there is an urgent need for new therapeutic interventions. Preclinical and initial human studies indicate that the GLP-1 receptor agonist semaglutide might reduce alcohol drinking. This study evaluated the efficacy of semaglutide once-weekly in treatment-seeking patients with alcohol use disorder and comorbid obesity.MethodsIn a 26-week, single-centre, randomised, double-blinded, placebo-controlled trial, treatment-seeking participants with moderate to severe alcohol use disorder and comorbid obesity were assigned (1:1) to receive once-weekly semaglutide (2·4 mg subcutaneously) or placebo (saline subcutaneously), in addition to standard cognitive behavioural therapy. The primary endpoint was a reduction in the number of heavy drinking days assessed after 26 weeks of intervention, analysed with an ANCOVA model. Analysis adhered to the intention-to-treat principle, and missing outcome data were addressed using multiple imputations. Safety was assessed in all treated patients. The trial is registered at ClinicalTrials.govNCT05895643, and is complete.FindingsFrom June 10, 2023, to Feb 4, 2025, 108 participants (53 women and 55 men) were enrolled, with 54 participants in each of the semaglutide and placebo treatment groups, and all were included in the data analysis. Overall, 88 participants (81%) completed the full intervention. Semaglutide was associated with a reduction in heavy drinking days (-41·1 percentage points from baseline, 95% CI -48·7 to -33·5) compared with placebo (-26·4, -34·1 to -18·6; estimated treatment difference -13·7 percentage points, -22·0 to -5·4; p=0·0015), and had substantial effects on multiple secondary alcohol-related and somatic outcomes. Adverse events were transient, generally mild to moderate gastrointestinal effects, and occurred more frequently in the semaglutide group.InterpretationSemaglutide showed robust therapeutic effects in treatment-seeking participants with obesity and alcohol use disorder and this trial supports previous preclinical and clinical findings suggesting GLP-1 receptor agonists as a potential novel treatment target for alcohol use disorder.FundingThe Research Foundation, Mental Health Services (Capital Region of Denmark), the Novo Nordisk Foundation, the Novavi Foundation, the Hartmann Foundation, and the Augustinus Foundation.

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

Results from this study2

2 results from studies that gave the peptide. 2 results from people.

01HumanRandomized controlled trialEfficacy outcome
In treatment-seeking adults with alcohol use disorder and obesity, semaglutide reduced heavy drinking days more than placebo after 26 weeks.
In plain wordsIn adults with alcohol use disorder and obesity, semaglutide cut heavy drinking days more than placebo over 26 weeks.
Peptide
Semaglutide
Outcome
DecreaseHeavy drinking days (change from baseline at 26 weeks)
Study
n = 108
Comparator
Placebo
Analysis
Primary
Outcome group
Addiction, withdrawal and alcohol intake · Mental health and mood
Studied dose
2.4 mg once weekly · subcutaneous · 26 weeksAs given in this study (human).
Measurements
Heavy drinking days change
−41.1 percentage points
semaglutide
Heavy drinking days change
−26.4 percentage points
placebo
Estimated treatment difference
−13.7 percentage points
semaglutide vs placebo
Source sentences
Summary
Semaglutide was associated with a reduction in heavy drinking days (-41·1 percentage points from baseline, 95% CI -48·7 to -33·5) compared with placebo (-26·4, -34·1 to -18·6; estimated treatment difference -13·7 percentage points, -22·0 to -5·4; p=0·0015)
1 context sentence(design, population, supporting numbers)
Summary · context
In a 26-week, single-centre, randomised, double-blinded, placebo-controlled trial, treatment-seeking participants with moderate to severe alcohol use disorder and comorbid obesity were assigned (1:1) to receive once-weekly semaglutide (2·4 mg subcutaneously) or placebo (saline subcutaneously), in addition to standard cognitive behavioural therapy.
Show in the study text Report a problemFND-4207057101
02HumanRandomized controlled trialSafety outcome
In adults with alcohol use disorder and obesity, transient, mostly mild to moderate gastrointestinal adverse events occurred more often with semaglutide than with placebo.
In plain wordsIn adults with alcohol use disorder and obesity, mild to moderate stomach and gut side effects were more common with semaglutide than placebo.
Peptide
Semaglutide
Outcome
IncreaseGastrointestinal adverse events
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
2.4 mg once weekly · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
Adverse events were transient, generally mild to moderate gastrointestinal effects, and occurred more frequently in the semaglutide group.
1 context sentence(design, population, supporting numbers)
Summary · context
In a 26-week, single-centre, randomised, double-blinded, placebo-controlled trial, treatment-seeking participants with moderate to severe alcohol use disorder and comorbid obesity were assigned (1:1) to receive once-weekly semaglutide (2·4 mg subcutaneously) or placebo (saline subcutaneously), in addition to standard cognitive behavioural therapy.
Show in the study text Report a problemFND-4207057102

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Registered trials1

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

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 2NCT05895643

Does Semaglutide Reduce Alcohol Intake in Patients With Alcohol Use Disorder and Comorbid Obesity?

Psychiatric Centre Rigshospitaletn = 10813 Jun 2023 to 31 Jul 2025

Alcohol Abuse · Alcohol Addiction · Alcohol Dependence · Alcohol Use Disorder

Trial page ClinicalTrials.govUpdated 5 Aug 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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