Semaglutide for Alcoholism

Overseen By Masoumeh Dejman

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute on Drug Abuse (NIDA)

Must not be taking: GLP-1 analogues, Insulin

Disqualifiers: Diabetes, Pancreatitis, Cirrhosis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 21

Duration: 20 weeks

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Semaglutide (known by brand names Ozempic, Wegovy, and Rybelsus) can safely help individuals with alcohol use disorder (AUD) reduce their alcohol consumption. Participants will receive either Semaglutide or a placebo (a harmless fake treatment) through weekly injections. The trial seeks adults with AUD who currently consume more than 7 drinks per week for females or 14 for males and experience frequent heavy drinking days (more than 3 or 4 drinks in one sitting). Participants will visit the research center weekly and engage in various activities, including questionnaires, taste tests, and virtual reality experiences, over approximately 5 months. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including those for lowering glucose, weight-loss drugs, and FDA-approved treatments for alcohol use disorder, at least 30 days before participating. If you are on any of these medications, you will need to stop them to join the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that semaglutide is generally well-tolerated. In earlier research, adults who took semaglutide for 9 weeks experienced some reduction in alcohol cravings without major side effects. This suggests the treatment is reasonably safe for short-term use.

While researchers continue to test semaglutide for alcohol use disorder, the FDA has already approved it for other conditions like diabetes and weight management. This approval indicates that its safety is well-understood for those uses. As with any medication, some people may experience side effects, but its use in other conditions provides a better understanding of its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for alcoholism?

Most treatments for alcoholism focus on behavioral therapy or medications like naltrexone, acamprosate, and disulfiram, which alter brain chemicals involved in alcohol dependence. But semaglutide works differently, targeting the GLP-1 receptor, which is primarily used for managing diabetes and obesity. Researchers are excited about semaglutide because early studies suggest it might reduce alcohol cravings and consumption by affecting brain pathways related to reward and addiction. Additionally, semaglutide is administered through weekly injections, which may improve adherence compared to daily medications. This unique approach could offer a new, effective option for individuals struggling with alcoholism.

What evidence suggests that Semaglutide might be an effective treatment for alcohol use disorder?

Research shows that semaglutide, which participants in this trial may receive, may help reduce the desire to drink and some drinking habits in people with alcohol use disorder (AUD). Earlier studies found that it lowered the urge to drink and reduced episodes of heavy drinking. Semaglutide, primarily used to treat diabetes and obesity, appears to alter the brain's response to alcohol, possibly by slowing alcohol's entry into the bloodstream. This effect could help people with AUD drink less. Although more research is needed, these early findings offer promise for those seeking new treatment options. ^{1 3 4 5 6}

Who Is on the Research Team?

Lorenzo Leggio, M.D.

Principal Investigator

National Institute on Drug Abuse (NIDA)

Are You a Good Fit for This Trial?

Adults aged 18 or older with Alcohol Use Disorder (AUD) who drink more than a moderate amount weekly and can understand English may join. They shouldn't be on other AUD treatments, have unstable heart conditions, extreme body weight, certain blood test abnormalities, diabetes, or be pregnant. Those with specific medical histories like thyroid cancer or severe allergies to similar drugs are excluded.

Inclusion Criteria

Able to speak, read, write, and understand English as demonstrated by ability to understand and sign the NIDA screening protocol consent

I drink more than the recommended weekly limit for my gender.

You are an adult who has been diagnosed with alcohol use disorder (AUD).

Exclusion Criteria

I have diabetes or my HbA1c level is 6.5% or higher.

I am currently using FDA-approved medication for alcohol use disorder.

I or my family have a history of MTC or MEN 2.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly subcutaneous injections of semaglutide or placebo for 20 weeks

20 weeks

20 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Semaglutide
• Take Control

Trial Overview The STAR trial is testing if Semaglutide can safely help reduce alcohol consumption in people with AUD. Participants will randomly receive either Semaglutide or a placebo as weekly shots for about 5 months at NIDA in Baltimore and undergo tests including blood work, therapy sessions, questionnaires, taste tests, virtual reality experiences and brain scans.

How Is the Trial Designed?

Group I: Semaglutide Experimental Treatment 2 Interventions

Weekly subcutaneous (s.c.) injections of semaglutide up to 2.4 mg/week or maximum tolerated dose (MTD). Consistent with current recommendations, the dose will be titrated at minimum every four weeks to maximize tolerability and minimize adverse events.

Group II: Placebo Placebo Group 1 Intervention

Weekly subcutaneous (s.c.) injections of placebo.

Semaglutide is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Canada as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Japan as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Wegovy for:

• Obesity

Approved in United States as Rybelsus for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

National Institute on Drug Abuse (NIDA)

Lead Sponsor

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

Semaglutide, a GLP-1 receptor agonist with a long half-life, effectively promotes insulin secretion in a glucose-dependent manner, making it a valuable treatment for type 2 diabetes, approved for use worldwide and in Japan since 2018.

Oral semaglutide (Rybelsus®) is the first GLP-1 receptor agonist available in pill form, showing continuous benefits in glycemic control for patients with type 2 diabetes across various stages, as demonstrated in multiple global clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New drug for type 2 diabetes: introduction of oral Semaglutide (Rybelsus® tablets), an oral GLP-1 receptor agonist]. Miyasaka, K.[2022]

In a meta-analysis of 23 randomized trials involving 22,096 patients with type 2 diabetes, semaglutide was not found to significantly increase the overall risk of diabetic retinopathy (DR) compared to control groups.

However, the analysis indicated that semaglutide was associated with a higher risk of DR in specific subgroups, particularly in patients aged 60 years or older and those with a diabetes duration of 10 years or more, suggesting that caution is warranted in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials. Wang, F., Mao, Y., Wang, H., et al.[2022]

Semaglutide, a GLP-1 receptor agonist for type 2 diabetes, has a good safety profile but is associated with a high prevalence of gastrointestinal disorders, reported in over 3500 cases (53.2%).

Compared to other diabetes medications like sitagliptin and empagliflozin, semaglutide has a significantly higher number of reported gastrointestinal adverse events, indicating the need for careful monitoring in certain patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. Cabral Lopes, A., Roque, F., Lourenço, O., et al.[2023]

Oral semaglutide, particularly at doses of 14 mg or flexibly dosed, significantly reduced HbA1c levels and body weight in patients with type 2 diabetes compared to other treatments, especially in those with higher baseline HbA1c levels.

The safety profile of oral semaglutide was comparable to that of other treatments, although it was associated with a higher incidence of gastrointestinal adverse events, which were consistent across different patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. Aroda, VR., Bauer, R., Christiansen, E., et al.[2022]

Semaglutide (Ozempic®) is an effective once-weekly treatment for type 2 diabetes, showing superior glucose-lowering effects and greater weight loss compared to other GLP-1 receptor agonists in Phase III clinical trials.

It is approved for use in Belgium for patients with type 2 diabetes who have not achieved adequate control with other antidiabetic therapies, particularly in those with a body mass index of 30 kg/m² or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. Scheen, AJ.[2019]

In a pooled analysis of phase 3a trials involving patients with type 2 diabetes, semaglutide demonstrated significant reductions in HbA1c and body weight, with greater efficacy observed in patients with higher baseline HbA1c levels.

The safety profile of semaglutide was consistent with other GLP-1 receptor agonists, primarily featuring gastrointestinal side effects, indicating it is a safe option for a wide range of patients with varying diabetes characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of baseline characteristics and beta-cell function on the efficacy and safety of subcutaneous once-weekly semaglutide: A patient-level, pooled analysis of the SUSTAIN 1-5 trials. Aroda, VR., Capehorn, MS., Chaykin, L., et al.[2022]

Citations

1. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2829811

Once-Weekly Semaglutide in Adults With Alcohol Use ... Over 9 weeks of treatment, semaglutide led to reductions in some but not all measures of weekly consumption, significantly reduced weekly alcohol craving ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39937469/

Once-Weekly Semaglutide in Adults With Alcohol Use Disorder These findings provide initial prospective evidence that low-dose semaglutide can reduce craving and some drinking outcomes.

3. bbrfoundation.org bbrfoundation.org/content/glp-1-drug-semaglutide-ozempic-wegovy-reduced-heavy-drinking-craving-adults-alcohol-use

GLP-1 Drug Semaglutide (Ozempic, Wegovy) Reduced ... GLP-1 Drug Semaglutide (Ozempic, Wegovy) Reduced Heavy Drinking & Craving in Adults with Alcohol Use Disorder. Posted: July 24, 2025. GLP-1 ...

4. news.vt.edu news.vt.edu/articles/2025/10/research_fralinbiomed_difeglp1au.html

Ozempic, Wegovy may help reduce alcohol use So if GLP-1s slow alcohol entering the bloodstream, they could reduce the effects of alcohol and help people drink less.” More than half of U.S. ...

5. nature.com nature.com/articles/s41467-024-48780-6

Associations of semaglutide with incidence and recurrence ... Given that the previous clinical trial of the GLP-1RA exenatide for AUD found reduced alcohol consumption only in those who were overweight, we ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11822619/

Once-Weekly Semaglutide in Adults With Alcohol Use Disorder Over 9 weeks of treatment, semaglutide led to reductions in some but not all measures of weekly consumption, significantly reduced weekly ...