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

135 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing oral semaglutide, a medication taken by mouth, to see if it can help people with Alcohol Use Disorder (AUD) reduce their cravings and drinking. Researchers want to see if semaglutide is safe and if it changes how the brain responds to alcohol cues. Semaglutide was initially developed for the treatment of type 2 diabetes and has shown efficacy in weight loss for individuals with and without diabetes.

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.

What evidence supports the effectiveness of the drug semaglutide for treating alcoholism?

Research shows that semaglutide, a drug originally used for weight loss and diabetes, has helped reduce alcohol use disorder symptoms in some patients and decreased alcohol intake in animal studies. This suggests it might be effective for treating alcoholism. ^{1 2 3 4 5}

Is semaglutide safe for humans?

Semaglutide has been studied for safety in people with type 2 diabetes and has shown a tolerable safety profile, similar to other drugs in its class. Some common side effects include gastrointestinal issues, but its cardiovascular safety is comparable to a placebo in high-risk patients. ^{2 4 6 7 8}

How is the drug Semaglutide unique in treating alcoholism?

Semaglutide is unique in treating alcoholism because it is primarily known for its use in managing diabetes and obesity, working by mimicking a hormone that regulates appetite and insulin levels, which is different from traditional alcohol dependence treatments that often target the brain's reward system. ^{9 10 11 12 13}

Research Team

Joseph P Schacht, PhD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

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.

Able to read and understand questionnaires and informed consent

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission. [2023]

2. Belgium pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

GREATER COMBINED REDUCTIONS IN HbA1C &#8805;1.0% AND WEIGHT &#8805;5.0% WITH SEMAGLUTIDE VERSUS COMPARATORS IN TYPE 2 DIABETES. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Significant Decrease in Alcohol Use Disorder Symptoms Secondary to Semaglutide Therapy for Weight Loss: A Case Series. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Semaglutide reduces alcohol intake and relapse-like drinking in male and female rats. [2023]

6. Belgium pubmed.ncbi.nlm.nih.gov

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

7. England 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sodium oxybate in alcohol-dependent patients with a very high drinking risk level. [2019]

10. New Zealand pubmed.ncbi.nlm.nih.gov

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

11. Switzerland 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. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Sodium oxybate plus nalmefene for the treatment of alcohol use disorder: A case series. [2016]

13. United States pubmed.ncbi.nlm.nih.gov

Sodium oxybate for narcolepsy with cataplexy: systematic review and meta-analysis. [2022]