Semaglutide for Alcohol Use Disorder

NCT05520775 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 21-1689R21AA026931-02
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Alcohol Use Disorder; Cigarette Smoking

Outcome Measures

Primary Outcomes (2)

• Change in Alcohol Consumed

  Estimated grams of ethanol consumed.

  Baseline (Week 0) to post-medication (Week 8)

• Change in Breath Alcohol Concentration

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

  Baseline (Week 0) to post-medication (Week 8)

Secondary Outcomes (6)

• Change in Subjective Stimulation (Biphasic Alcohol Effects Scale)

  Baseline (Week 0) to post-treatment (Week 8)

• Change in Subjective Sedation (Biphasic Alcohol Effects Scale)

  baseline (Week 0) to post-medication (Week 8)

• Change in Alcohol Demand (Alcohol Purchase Task)

  Baseline (Week 0) to post-treatment (Week 8)

• Change in Cigarette Demand (Cigarette Purchase Task)

  Baseline (Week 0) to Post-medication (Week 8)

• Change in Daily Alcohol Use

  baseline (Week 0) to study endpoint (Week 10)

Other Outcomes (3)

• Change in Weight

  baseline (Week 0) to study endpoint (Week 10)

• Change in HbA1c

  baseline (Week 0) to study endpoint (Week 10)

• Change in Alcohol Elimination

  baseline (Week 0) to post-medication (Week 8)

Study Arms (2)

Semaglutide

EXPERIMENTAL

Participants will receive semaglutide via subcutaneous injections at escalating doses (.25mg to 1.0mg) over 9 weeks.

Drug: Semaglutide

Sham/Placebo

SHAM COMPARATOR

Participants will receive sham subcutaneous injections over 9 weeks.

Drug: Sham/placebo

Interventions

Semaglutide DRUG

Semaglutide (subcutaneous)

Semaglutide

Sham/placebo DRUG

Sham subcutaneous injection

Sham/Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 21-65
• Meeting DSM-5 criteria for current (past year) alcohol use disorder (with 2-7 symptoms endorsed) and National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria for current at-risk drinking (i.e., \>7/14 drinks in one week for women/men, with at least two episodes of 4+/5+ drinks in the past 30 days)
• Willingness/availability to take study medication and complete study procedures, including attending weekly visits for medication administration, side effect assessments, and glucose monitoring
• Willingness to complete laboratory sessions involving alcohol administration
• Ability to communicate and read in English

You may not qualify if:

• Reporting past 30-day use of illicit drugs other than cannabis at baseline, or having a positive toxicology screen for illicit drugs other than cannabis at baseline
• Meeting past-year criteria for a substance use disorder (with the exception of alcohol, tobacco or mild cannabis use disorder)
• Current engagement in alcohol treatments, or currently engaged in intentional efforts to quit alcohol use
• Past 30-day use of: Sincalide, Sulfonylureas, insulin and insulin products or other medications that may interact with semaglutide;, or weight control medications
• Prior use of semaglutide or other GLP-1 agonists
• Known or suspected hypersensitivity to study medication or related products
• Lifetime diagnosis of severe mental illness (including schizophrenia and bipolar disorder)
• History of suicide attempt, or recent (past 30 day) suicidal ideation, or psychiatric hospitalization in the last 6 months
• Current significant medical or neurological illness (based on self-report or medical record) including severe hepatic impairment or cirrhosis, impaired renal function (eGFR \<50ml/min), acute or chronic pancreatitis, gastroparesis, gallbladder disease or cholelithiasis, other severe gastrointestinal disease, heart failure, coronary artery disease, stroke, seizure disorder, or other medical condition that poses a risk for the medication or alcohol administration components of the study (as determined by the MD)
• A personal or family history of medullary thyroid cancer or multiple endocrine neoplasia 2A or 2B
• Calcitonin greater than or equal to 50 ng/L
• Uncontrolled thyroid disease at screening
• History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g., subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)
• History of Type 1 or Type 2 diabetes, or HbA1c \>6.5% measured at screening
• History of diabetic retinopathy, proliferative retinopathy, or maculopathy

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

UNC-Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• 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. Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2025 Apr 1;82(4):395-405. doi: 10.1001/jamapsychiatry.2024.4789.

  PMID: 39937469 DERIVED

MeSH Terms

Conditions

Alcoholism; Cigarette Smoking

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Tobacco Smoking; Smoking; Behavior; Tobacco Use

Results Point of Contact

• Title: Christian Hendershot
• Organization: University of North Carolina at Chapel Hill

christian.hendershot@usc.edu

(213) 821-0769

Study Officials

• Christian Hendershot, Ph.D.

  UNC-Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized parallel group design.

Study Record Dates

• First Submitted: August 26, 2022
• First Posted: August 30, 2022
• Study Start: September 2, 2022
• Primary Completion: April 12, 2024
• Study Completion: April 19, 2024
• Last Updated: April 2, 2025
• Results First Posted: March 24, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will become available following publication of study manuscripts and will be available indefinitely.
• Access Criteria: Reasonable request from qualified investigator.

Locations

US (1)