Cessation or Reduction of Alcohol Consumption in Veterans: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial to Evaluate the Efficacy and Safety of a GLP-1 Receptor Agonist Semaglutide in U.S. Veterans With Alcohol Use Disorder

NCT07218354 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 2041
• Study Type: interventional
• Target: 622
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial aims to test the effectiveness and safety of semaglutide, a GLP-1 receptor agonist, in treating moderate to severe alcohol use disorder (AUD) in Veterans. Participants who qualify will be randomly assigned to receive either semaglutide injections or placebo injections over a 28-week period, followed by a 4-week post-treatment safety assessment period. Participants receiving semaglutide will start with a low dose, gradually increasing to a maximum of 2.4 mg per week, depending on their tolerance. The primary measure of success will be a reduction in risky drinking, assessed through a reliable calendar-based interview method called the Timeline Follow-Back (TLFB), a well-validated calendar-based interview technique for recording daily alcohol consumption. The purpose of this research is to gather information on the effectiveness of semaglutide for treating AUD, potentially offering a new and more appealing treatment option.

Conditions

Alcohol Use Disorder

Keywords

Alcohol use Disorder; Semaglutide; Alcohol; GLP-1

Outcome Measures

Primary Outcomes (1)

• Two-level reduction in the World Health Organization (WHO) risk drinking level

  Number of participants with at least a two-level reduction, from baseline risk level, in WHO risk drinking level. The WHO risk drinking levels categorize alcohol consumption into four groups: low (level 1; 0-2.86 standard drinks/day for men; 0-1.43 drinks/day for women), moderate (level 2; 2.87-4.29 standard drinks/day for men; 1.44-2.86 drinks/day for women), high (level 3; 4.3-7.14 standard drinks/day for men; 2.87-4.29 drinks/day for women), and very high (level 4; \>7.15 drinks/day for men; \>4.3 drinks/day for women). One standard drink is 14g of alcohol. A 2-level reduction, such as moving from very high to moderate risk, is considered a significant clinical improvement.

  Change from Baseline to Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28.

Secondary Outcomes (12)

• Adverse events of special interest (Assessing safety and tolerability)

  From randomization through week 32.

• No heavy drinking days

  Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28.

• Two-level reduction in the World Health Organization (WHO) risk drinking level by Race category

  Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28.

• Two-level reduction in the World Health Organization (WHO) risk drinking level by age category (<65, ≥ 65) at baseline

  Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28.

• Two-level reduction in the World Health Organization (WHO) risk drinking level by psychiatric comorbidity at baseline

  Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28.

Study Arms (2)

Semaglutide

EXPERIMENTAL

Weekly subcutaneous injections of semaglutide up to 2.4 mg/week or maximum tolerated dose. Initial dosing starting at 0.25 for weeks 1-4. Further titration up to 2.4 mg weekly starting at week 5.

Drug: Semaglutide

Placebo

PLACEBO COMPARATOR

Weekly subcutaneous injections of placebo.

Drug: Placebo

Interventions

Semaglutide DRUG

Weekly subcutaneous injections of semaglutide up to 2.4 mg/week or maximum tolerated dose. Initial dosing starting at 0.25 for weeks 1-4. Further titration up to 2.4 mg weekly starting at week 5.

Semaglutide

Placebo DRUG

Weekly subcutaneous injections of placebo.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Veteran.
• WHO risk drinking level of Very High or High in the 30 days prior to screening.
• Current diagnosis of moderate or severe AUD (i.e., meeting at least 4 of 11 DSM-5 AUD criteria) based on semi-structured diagnostic exam.
• Able and willing to provide informed consent.

You may not qualify if:

• Medical and Psychiatric:
• Type 1 diabetes.
• Current serious psychiatric illness (i.e., schizophrenia, bipolar disorder, severe or psychotic major depression, borderline or antisocial personality disorder, eating disorder).
• Current DSM-5 diagnosis of a SUD (other than moderate-to-severe alcohol, any nicotine, or mild cannabis use disorders).
• At the time of randomization, moderate-to-severe alcohol withdrawal (Clinical Institute Withdrawal Assessment for Alcohol (CIWA-AR) \>8).
• BMI \<21 kg/m2.
• Unstable body weight defined as \>5% change in body weight (documented or self-report; intentional or not) in the 90 days prior to randomization.
• History of acute or chronic pancreatitis.
• History of diabetic ketoacidosis.
• History of proliferative diabetic retinopathy.
• History of ascites, advanced liver fibrosis, compensated cirrhosis with portal hypertension, decompensated cirrhosis, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or hepatocellular carcinoma (HCC).
• History of stage 3 fibrosis or stage 4 cirrhosis from a liver biopsy.
• Presence of gastroparesis.
• History of acute gallbladder disease in the prior 6 months.
• History of advanced fibrosis or cirrhosis, including (but not limited to) transient elastography (liver stiffness) of \>12 kPa, FIB-4 2.67, ELF 9.8, MRE 3.63 kPa.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Philadelphia, Pennsylvania, 19104-4551, 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

• David W. Oslin, MD

  Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

  STUDY CHAIR

Central Study Contacts

David W Oslin, MD

CONTACT

(215) 823-5870; Dave.Oslin@va.gov

Neil C Johnson, MA BA

CONTACT

(702) 202-8387; neil.johnson@va.gov

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants assigned to the placebo group will receive a placebo pen, which mimics the treatment pens by following the same treatment procedure.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Participants are randomized 1:1 to either Semaglutide or Placebo injections. The Semaglutide group will be titrated from 0.25 mg up to 2.4 mg/week based on flexible dosing.

Study Record Dates

• First Submitted: September 23, 2025
• First Posted: October 20, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): April 28, 2028
• Study Completion (Estimated): May 26, 2029
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

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

Locations

US (1)