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

NCT05895643 | Completed Phase 2 DMC

• 2 other identifiers: The SEMALCO studyU1111-1286-6919
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

This 26-week long, double-blinded randomized clinical trial aims to investigate the effects of the GLP-1 receptor agonist semaglutide s.c. vs placebo on alcohol consumption in 108 patients diagnosed with alcohol use disorder and comorbid obesity (BMI\>30 kg/m2). Patients will be treated for 26 weeks with semaglutide subcutaneously (s.c.) once weekly or placebo. The medication will be provided as a supplement to standardised cognitive behavioural therapy. A subgroup of the patients will have two brain scans (Magnetic Resonance Spectroscopy (MRS) and functional Magnetic Resonance Imaging (fMRI)) conducted in one scan session at week 0 and 26. The primary endpoint is the percentage-point reduction in total number of heavy drinking days, defined as days with an excess intake of 48/60 grams of alcohol per day (women and men, respectively) from baseline to follow-up after 26 weeks of treatment, measured by the timeline followback (TLFB) method.

Conditions

Alcohol Abuse; Alcohol Addiction; Alcohol Dependence; Alcohol Use Disorder

Keywords

GLP-1; Glucagon-like peptide 1; semaglutide; fMRI; MRS

Outcome Measures

Primary Outcomes (1)

• Change in heavy drinking days

  Change in alcohol consumption, defined as the change in percentage of heavy drinking days during a period of 30 consecutive days, after 26 weeks of treatment adjusted for baseline (percentage points (pp)). A heavy drinking day is defined as more than 60/48 grams (men/women) of alcohol in one day, measured with the validated timeline follow-back (TLFB) method.

  From baseline to 26 weeks of treatment

Secondary Outcomes (25)

• Change in heavy drinking days adjusted for maximum tolerable semaglutide dose given

  From baseline to 26 weeks of treatment

• Change in heavy drinking days adjusted for weightloss

  From baseline to 26 weeks of treatment

• Total alcohol consumption

  From baseline to 26 weeks of treatment

• Drinks per day

  From baseline to 26 weeks of treatment

• Days without alcohol consumption

  From baseline to 26 weeks of treatment

Study Arms (2)

semaglutide

EXPERIMENTAL

Wegovy once-weekly s.c.titrated to a maximum dose of 2.4 mg

Drug: Semaglutide Injectable Product

placebo

PLACEBO COMPARATOR

Saline s.c. once-weekly

Drug: Placebo

Interventions

Semaglutide Injectable Product DRUG

Once weekly injections s.c with semaglutide (Wegovy)

Also known as: Wegovy

semaglutide

Placebo DRUG

Once weekly injections s.c with placebo (BD Posiflush)

Also known as: BD Posiflush (saline)

placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed oral and written consent
• Diagnosed with alcohol dependence according to the criteria of the International Classification of Diseases 10 (ICD-10), and diagnosed with alcohol use disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
• Alcohol use disorder identification test (AUDIT) score \>15
• Body mass index (BMI) above or equal to 30 kg/m2
• Age 18 - 70 years (both included)
• Heavy alcohol drinking defined as more than 6 days with alcohol consumption over 4 units (48 g alcohol) for women and 5 units (60 g alcohol) for men during a consecutive 30-day period, within 40 days prior to baseline evaluation, measured by the TLFB method. The 30-day period will be the 30 consecutive days with the biggest alcohol intake (most heavy drinking days and the largest amount of total alcohol) out of the 40 days.

You may not qualify if:

• Severe psychiatric disease, defined as a diagnosis of schizophrenia, paranoid psychosis, bipolar disorder or mental retardation
• A history of delirium tremens or alcohol withdrawal seizures
• Present or former neurological disease, including traumatic brain injury
• Females of childbearing potential who are pregnant, breast-feeding or have the intention of becoming pregnant within the next 9 months (26 weeks plus two months after discontinuation of semaglutide), or are not using contraceptives (during the whole study period) considered as highly effective (combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) intrauterine device, bilateral tubal occlusion, vasectomised partner, sexual abstinence).
• Impaired hepatic function (liver transaminases \>3 times the upper limit)
• Impaired renal function (eGFR \< 50 ml/min and/or plasma creatinine \>150 μmol/l)
• Impaired pancreatic function (any history of acute or chronic pancreatitis and/or amylase \> 2 times upper limit)
• Former medullary thyroid carcinoma (MTC) and/or family history with MTC and/or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• Cardiac problems defined as decompensated heart failure (NYHA class III or IV), unstable angina pectoris and/or myocardial infarction within the last 12 months
• Uncontrolled hypertension (systolic blood pressure \>180 mmHg, diastolic blood pressure \>110 mmHg)
• Receiving any investigational drug within the last three months
• Use of weight-lowering pharmacotherapy within the preceding 3 months
• Any other active substance use defined as a DUDIT-score \>1 (except nicotine)
• Hypersensitivity to the active substance or any of the excipients
• Only for patients undergoing brain scans:

Sponsors & Collaborators

• Psychiatric Centre Rigshospitalet: lead
• Neurobiology Research Unit: collaborator

Study Sites (1)

Psychiatric Center Copenhagen, Frederiksberg Hospital

Frederiksberg, 2000, Denmark

Location

Related Publications (2)

• Jensen ME, Klausen MK, Bergmann ML, Knudsen GM, Vilsboll T, Stove C, Fink-Jensen A. Blood phosphatidylethanol measurements indicate GLP-1 receptor stimulation causes delayed decreases in alcohol consumption. Alcohol Clin Exp Res (Hoboken). 2025 May;49(5):1161-1165. doi: 10.1111/acer.70041. Epub 2025 Mar 23.

  PMID: 40123107 DERIVED

• Klausen MK, Kuzey T, Pedersen JN, Justesen SK, Rasmussen L, Knorr UB, Mason G, Ekstrom CT, Holst JJ, Koob G, Benveniste H, Volkow ND, Knudsen GM, Vilsboll T, Fink-Jensen A. Does semaglutide reduce alcohol intake in Danish patients with alcohol use disorder and comorbid obesity? Trial protocol of a randomised, double-blinded, placebo-controlled clinical trial (the SEMALCO trial). BMJ Open. 2025 Jan 8;15(1):e086454. doi: 10.1136/bmjopen-2024-086454.

  PMID: 39779270 DERIVED

MeSH Terms

Conditions

Alcoholism

Interventions

semaglutide; Sodium Chloride

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Anders Fink-Jensen, MD, DMSc

  Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 26, 2023
• First Posted: June 8, 2023
• Study Start: June 13, 2023
• Primary Completion: July 31, 2025
• Study Completion: July 31, 2025
• Last Updated: August 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

DK (1)