Semaglutide for Alcoholism

Overseen By Kristen M Raymond

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Psychotropics, AUD meds, Weight control, Metformin

Disqualifiers: Substance use disorder, Bipolar, Diabetes, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether semaglutide (also known as Ozempic, Wegovy, or Rybelsus) can help reduce alcohol cravings and consumption. It compares the safety and effectiveness of the medication to a placebo (a pill with no active ingredient) in individuals aiming to reduce their drinking. Participants will take either semaglutide or a placebo for eight weeks. This trial may suit someone with moderate to severe alcohol use disorder who actively seeks treatment and struggles with alcohol cravings. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important research.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications, such as AUD pharmacotherapy (like naltrexone, acamprosate, or disulfiram) and weight control medications, at least a month before starting. If you're on antidepressants, your dose must be stable for at least two months. Please check with the clinical site for more details.

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

Research shows that semaglutide, a medication often used for diabetes and weight management, might also help people with alcohol use disorder (AUD). Earlier studies found semaglutide promising in reducing alcohol cravings and heavy drinking. These studies did not identify any serious safety issues, suggesting the drug is generally safe.

Participants in these studies often experienced mild side effects like nausea, which is common with semaglutide. Notably, the FDA has already approved this drug for other uses, such as controlling blood sugar and aiding weight loss, supporting its safety in humans.

While this trial specifically tests semaglutide for AUD, safety results from other uses suggest it may be safe for this purpose too. Participants should still consider these findings and consult healthcare professionals before joining the trial. ^{1 2 3 4 5}

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

Unlike the standard treatments for alcoholism, which often include behavioral therapies and medications such as naltrexone or disulfiram, semaglutide presents a novel approach by targeting the GLP-1 receptor. Originally designed to treat type 2 diabetes, semaglutide helps regulate blood sugar levels and, intriguingly, may also influence the brain's reward system linked to alcohol consumption. Researchers are excited about semaglutide because it offers a new mechanism of action that could reduce cravings and improve treatment outcomes for those struggling with alcohol dependency.

What evidence suggests that semaglutide might be an effective treatment for alcoholism?

Research has shown that semaglutide, initially used for diabetes and weight loss, might help reduce alcohol cravings and consumption in people with Alcohol Use Disorder (AUD). One study found that semaglutide significantly lowered weekly alcohol cravings and some drinking habits. Another study found it led to less heavy drinking and fewer cravings. The drug slows the rate at which alcohol enters the bloodstream, potentially reducing its effects and helping people drink less. In this trial, participants will receive either semaglutide or a placebo to evaluate its effectiveness in managing AUD. ^{1 3 4 5 6}

Who Is on the Research Team?

Joseph P Schacht, PhD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

Adults over 21 with Alcohol Use Disorder seeking treatment, having a BMI of at least 25 kg/m2, and living within 50 miles of the study site. Excluded are those with certain mental health conditions, using specific medications or therapies for AUD or weight control, past use of GLP-1 agonists like semaglutide, severe alcohol withdrawal history, diabetes, kidney disease, gastrointestinal diseases including pancreatitis, uncontrolled hypertension or liver issues.

Inclusion Criteria

I am 21 years old or older.

Meets DSM-5 criteria for current AUD of at least moderate severity, as assessed by MINI

Able to read and understand questionnaires and informed consent

Exclusion Criteria

Current DSM-5 diagnosis of any other substance use disorder of moderate or greater severity, except for Nicotine Use Disorder, as assessed by MINI

Current or lifetime eating disorder (anorexia, bulimia, or binge eating disorder) or psychotic disorder, as assessed by MINI

I have been taking metformin in the past month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive semaglutide or placebo for 8 weeks, with dose titration and weekly to biweekly visits

8 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Semaglutide

Trial Overview The trial tests oral semaglutide (up to 7 mg daily) against a placebo in individuals with AUD for its safety and effects on craving and consumption of alcohol. This is an 8-week randomized controlled trial where participants are chosen by chance to receive either the drug or placebo.

How Is the Trial Designed?

Group I: Semaglutide 3 milligrams and 7 milligrams Active Control 2 Interventions

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.

Group II: Placebo Placebo Group 1 Intervention

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.

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?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

Sodium oxybate has shown significant efficacy in preventing alcohol relapse, particularly in patients with very high drinking risk levels, with abstinence rates increasing by up to 34% compared to placebo in large clinical trials involving 810 participants.

Despite its potential for abuse, sodium oxybate has been reported to have very few adverse side effects in a pharmacovigilance database of over 260,000 alcohol-dependent patients, indicating it is a well-tolerated and safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sodium oxybate in alcohol-dependent patients with a very high drinking risk level. van den Brink, W., Addolorato, G., Aubin, HJ., et al.[2019]

Sodium oxybate (SXB) significantly reduces cataplexy attacks and daytime sleepiness in adults with narcolepsy-cataplexy, based on a systematic review of 6 randomized controlled trials involving various efficacy measures.

While SXB is effective, it is associated with a higher incidence of mild to moderate adverse events, such as nausea and dizziness, compared to placebo, indicating that while it is generally well tolerated, patients should be monitored for these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium oxybate for narcolepsy with cataplexy: systematic review and meta-analysis. Alshaikh, MK., Tricco, AC., Tashkandi, M., et al.[2022]

In a post hoc analysis of 5,119 subjects from the SUSTAIN clinical trials, semaglutide (0.5 and 1.0 mg) led to significantly higher rates of achieving both ≥1.0% HbA1c reduction and ≥5.0% weight loss compared to other diabetes treatments, with rates ranging from 25% to 59% for semaglutide versus 2% to 23% for comparators.

Semaglutide was well tolerated and exhibited a safety profile similar to other GLP-1 receptor agonists, indicating it is a safe and effective option for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GREATER COMBINED REDUCTIONS IN HbA1C ≥1.0% AND WEIGHT ≥5.0% WITH SEMAGLUTIDE VERSUS COMPARATORS IN TYPE 2 DIABETES. Rodbard, HW., Bellary, S., Hramiak, I., et al.[2022]

Semaglutide, a GLP-1 receptor agonist, significantly reduced alcohol intake and prevented relapse-like drinking in both male and female rats, suggesting its potential as a treatment for alcohol use disorder.

The mechanism appears to involve a reduction in alcohol-induced reward pathways, as semaglutide decreased dopamine release in the nucleus accumbens and altered dopamine metabolite levels, indicating its effects on the brain's reward system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide reduces alcohol intake and relapse-like drinking in male and female rats. Aranäs, C., Edvardsson, CE., Shevchouk, OT., et al.[2023]

Nalmefene, an opioid system modulator, has been shown to significantly reduce heavy drinking days and total alcohol consumption in alcohol-dependent adults when used as needed, based on results from two multinational trials (ESENSE 1 and ESENSE 2) and a longer-term study (SENSE).

The treatment was generally well tolerated, with common side effects including nausea, insomnia, and dizziness, making nalmefene a promising option for managing alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nalmefene: a review of its use in the treatment of alcohol dependence. Keating, GM.[2022]

In a case series of seven patients with alcohol use disorder who did not respond to sodium oxybate treatment, the addition of nalmefene led to significant improvements, including complete alcohol abstinence in two patients and reduced heavy drinking in five others during the first month.

Nalmefene may help modulate the reward effects of sodium oxybate, which could be contributing to ongoing alcohol consumption and cravings, suggesting a potential mechanism for its effectiveness, though further controlled trials are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium oxybate plus nalmefene for the treatment of alcohol use disorder: A case series. Caputo, F., Maremmani, AG., Addolorato, G., et al.[2016]

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 significantly reduced HbA1c levels in both non-elderly (1.2%-1.5%) and elderly (1.3%-1.5%) patients with type 2 diabetes compared to comparators, demonstrating its efficacy across age groups.

The safety profile of semaglutide was comparable in both age groups, with no increased risk of severe hypoglycemia, making it a suitable treatment option for elderly patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide as a therapeutic option for elderly patients with type 2 diabetes: Pooled analysis of the SUSTAIN 1-5 trials. Warren, M., Chaykin, L., Trachtenbarg, D., 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]

Semaglutide, a GLP-1 analogue, significantly reduced binge-like alcohol drinking in both male and female mice and rats, indicating its potential efficacy in treating alcohol use disorder (AUD).

The study also found that semaglutide enhanced GABA release in certain brain regions of alcohol-naive rats, suggesting a mechanism of action that could help regulate alcohol consumption, although it did not affect GABA transmission in alcohol-dependent rats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission. Chuong, V., Farokhnia, M., Khom, S., et al.[2023]

In a case series of 6 patients with alcohol use disorder (AUD) treated with semaglutide for weight loss, all patients showed significant improvement in AUD symptoms, with an average reduction of 9.5 points on the AUDIT scale (P < 0.001).

These findings suggest that glucagon-like peptide-1 receptor agonists (GLP-1RAs) like semaglutide may be a promising new treatment option for AUD, although further randomized clinical trials are necessary to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significant Decrease in Alcohol Use Disorder Symptoms Secondary to Semaglutide Therapy for Weight Loss: A Case Series. Richards, JR., Dorand, MF., Royal, K., et al.[2023]

In a 12-week study involving 378 adults with alcohol dependence, those taking nalmefene as needed significantly reduced their heavy drinking days by an average of 13.1 days per month, demonstrating its efficacy in lowering alcohol consumption.

The treatment was well tolerated, with common side effects including nausea (18.3%) and dizziness (17.7%), indicating that nalmefene can be a safe option for managing alcohol dependence in primary care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nalmefene, Given as Needed, in the Routine Treatment of Patients with Alcohol Dependence: An Interventional, Open-Label Study in Primary Care. Castera, P., Stewart, E., Großkopf, J., et al.[2019]

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]

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 ...