Clinical Trial of Rybelsus (Semaglutide) Among Adults With Alcohol Use Disorder (AUD)

NCT05892432 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 23-0261R21AA031146
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized controlled trial of oral semaglutide among treatment-seeking individuals with AUD. The investigators will randomly assign 50 participants to receive semaglutide (titrated to 7 milligrams (mg) per day) or matched placebo for 8 weeks. The primary aims are to assess the safety and tolerability of semaglutide in this population and to evaluate its effects, relative to placebo, on alcohol cue-elicited craving and alcohol consumption.

Conditions

Alcohol Use Disorder

Outcome Measures

Primary Outcomes (1)

• Change in Cue Craving Visual Analog Score

  The primary efficacy endpoint will be the magnitude of change between screening and Week 6 in the cue-craving VAS score on the first VAS item ("How strong is your craving to drink alcohol?") administered after the alcohol cue presentation. Scores range from 0 (none) to 20 (extremely strong). Higher scores indicate a higher level of craving.

  7 weeks - change between screening and Week 6 visit

Secondary Outcomes (3)

• Number of drinks per day

  4 weeks

• Percentage of heavy drinking days

  4 weeks

• Change in alcohol cue-elicited brain activation

  8 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants in this Arm will take a medically inert placebo. To ensure pill equivalence between groups, tablets will be packaged in the same capsule; thus, each participant will take one capsule per day. Participants will be instructed to ingest the capsule orally each morning.

Drug: Placebo

Semaglutide 3 milligrams and 7 milligrams

ACTIVE COMPARATOR

Participants in this Arm will study medication for a total of 8 weeks - on semaglutide 3 milligrams per day for 4 weeks, then 7 milligrams per day for 4 weeks. To ensure pill equivalence between groups, tablets will be packaged in the same capsule; thus, each participant will take one capsule per day. Participants will be instructed to ingest the capsule orally each morning.

Drug: Semaglutide 3 MG [Rybelsus]; Drug: Semaglutide 7 MG [Rybelsus]

Interventions

Semaglutide 3 MG [Rybelsus] DRUG

Semaglutide 3 mg will be taken for the first 4 weeks of the 8-week trial.

Also known as: Rybelsus 3 mg

Semaglutide 3 milligrams and 7 milligrams

Semaglutide 7 MG [Rybelsus] DRUG

Semaglutide 7 mg will be taken for the second 4 weeks of the 8-week trial.

Also known as: Rybelsus 7 mg

Semaglutide 3 milligrams and 7 milligrams

Placebo DRUG

A medically inert placebo medication will be taken for 8 weeks.

Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 21 or older.
• Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for current AUD of at least moderate severity, as assessed by the Mini International Neuropsychiatric Interview (MINI).
• Seeking pharmacological treatment for AUD and wants to stop or cut down on drinking.
• Has a body mass index (BMI) of at least 25 kg/m2.
• Able to read and understand questionnaires and informed consent.
• Lives within 50 miles of the study site.

You may not qualify if:

• Current DSM-5 diagnosis of any other substance use disorder of moderate or greater severity, except for Nicotine Use Disorder, as assessed by MINI.
• Urine drug screen at screening positive for any substance except cannabis.
• Current DSM-5 bipolar disorder, major depressive episode, or panic disorder, as assessed by MINI.
• Current or lifetime eating disorder (anorexia, bulimia, or binge eating disorder) or psychotic disorder, as assessed by MINI.
• Current suicidal ideation or homicidal ideation.
• Current use of other psychotropic medications except antidepressants (for which dose must be stable for at least the past 2 months).
• Current or past-month use of AUD pharmacotherapy, including (e.g., oral naltrexone, acamprosate, or disulfiram) or current or past 60-day use of injectable naltrexone.
• Current or past-month use of weight control medications.
• Current or past-month use of metformin for any indication.
• Any prior use of semaglutide or other GLP-1 agonists.
• History of severe alcohol withdrawal (e.g., seizure, delirium tremens), as evidenced by self- report and assessment with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar).
• Current or lifetime Type 1 or Type 2 diabetes diagnosis, or HbA1c \>6.5%.
• Current or lifetime kidney disease or creatinine clearance \<80 mL/min for participants \<=55 years of age (\<65 mL/min for those \>55).
• Personal history of gastrointestinal disease (e.g., gastroparesis) or pancreatitis.
• Personal or family history of medullary thyroid carcinoma and/or multiple endocrine neoplasia syndrome type 2

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Alcoholism

Interventions

semaglutide

Condition Hierarchy (Ancestors)

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

Study Officials

• Joseph P Schacht, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will be blind to medication assignment, as will all care providers and investigators.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind placebo controlled clinical trial.

Study Record Dates

• First Submitted: May 26, 2023
• First Posted: June 7, 2023
• Study Start: January 11, 2024
• Primary Completion: November 4, 2025
• Study Completion: November 15, 2025
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will become available 2 years after the grant end date, and will be available as long as the NDA exists.
• Access Criteria: Investigators at institutions with a Federal Wide Assurance (FWA) will be able to gain access to NDA data by submitting a data access request in accordance with applicable NDA policies. Data requests will be reviewed and granted by a NIAAA Data Access Committee.

Locations

US (1)