Semaglutide for Alcoholism

(STAR-T Trial)

Overseen by William K Simmons, Ph.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Oklahoma State University Center for Health Sciences

Must not be taking: GLP-1 analogues, Insulin, Naltrexone, others

Disqualifiers: Diabetes, Pancreatitis, Cardiovascular, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing if semaglutide, an injection given regularly, can help people with alcohol use disorder reduce their drinking. The medication might work by influencing the brain's reward system and appetite control. Semaglutide was originally approved for the treatment of type 2 diabetes and obesity, and has shown efficacy in weight loss.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining this trial. Specifically, you cannot use medications for diabetes, weight loss, or alcohol use disorder, and you should not be on medications that interact with semaglutide.

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 consumption in both animal studies and human case reports. People taking semaglutide reported less desire to drink and fewer heavy drinking days, suggesting 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, showing it is generally safe when used as directed. It has been tested in various forms, such as injections and oral tablets, and compared to placebo and other diabetes treatments, with safety data supporting its use. ^{1 2 6 7 8}

How does the drug Semaglutide differ from other treatments for alcoholism?

Semaglutide is unique because it is primarily used for managing diabetes and weight loss, and its potential use for alcoholism is novel. Unlike traditional treatments for alcoholism, which often focus on reducing cravings or withdrawal symptoms, Semaglutide works by mimicking a hormone that regulates appetite and blood sugar, which may indirectly influence alcohol consumption behaviors. ^{9 10 11 12 13}

Research Team

William K Simmons, Ph.D.

Principal Investigator

Oklahoma State University Center for Health Sciences

Eligibility Criteria

This trial is for adults with Alcohol Use Disorder who drink more than a moderate amount weekly and can consent to the study. They must be in stable health, not have certain mental health conditions or hearing loss, and women should use effective birth control. People with diabetes, severe kidney issues, high triglycerides, or those on specific medications cannot join.

Inclusion Criteria

I am following the required birth control and pregnancy testing guidelines.

Alcohol Use Disorder (minimum 2 symptoms on a validated diagnostic tool)

I am 18 years old or older.

Exclusion Criteria

Specific abnormal blood test results

Current or prior use of specific medications for AUD treatment

Any other reason or clinical condition that may interfere with study participation or safety

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 remote phone screening, 1 on-site visit

Treatment

Participants receive weekly subcutaneous injections of semaglutide or placebo with dose escalation over 12 weeks

12 weeks

Weekly visits for injections and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 weeks

1 remote follow-up assessment

Treatment Details

Interventions

• Placebo (Behavioural Intervention)
• Semaglutide (Glucagon-like peptide-1 receptor agonist)

Trial Overview The study tests if semaglutide can safely reduce alcohol consumption compared to a placebo (a substance with no therapeutic effect). Participants will receive either the actual drug or placebo without knowing which one they are getting.

Participant Groups

Group I: Semaglutide Experimental Treatment 1 Intervention

Participants will receive subcutaneous injections of semaglutide in escalating doses (.25mg to 1.0mg) over the course of 12 weeks.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive subcutaneous injections of a placebo saline solution over the course of 12 weeks.

Who Is Running the Clinical Trial?

Oklahoma State University Center for Health Sciences

Lead Sponsor

Trials

37

Recruited

4,900+

National Institute of Drug Abuse

Collaborator

Trials

11

Recruited

12,500+

Findings from Research

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]

A clinical trial is underway to investigate the efficacy of the GLP-1 receptor agonist exenatide in reducing heavy drinking days among 114 outpatients with alcohol dependence, supplementing cognitive-behavioral therapy over 26 weeks.

This study aims to provide new insights into medical treatments for alcohol dependence, as previous research has shown that GLP-1 receptor stimulation can reduce alcohol consumption in animal models, but its effects in humans have not been explored until now.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does glucagon-like peptide-1 (GLP-1) receptor agonist stimulation reduce alcohol intake in patients with alcohol dependence: study protocol of a randomised, double-blinded, placebo-controlled clinical trial. Antonsen, KK., Klausen, MK., Brunchmann, AS., et al.[2019]

A study involving 153 participants with obesity showed that those taking Semaglutide (a GLP-1 agonist) or Tirzepatide (a GLP-1/GIP agonist) reported significantly lower alcohol consumption and reduced cravings compared to those not on these medications.

Analysis of social media posts indicated that a majority of discussions around these medications highlighted their effects on reducing alcohol cravings, suggesting a potential new avenue for treating Alcohol Use Disorder in individuals with obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide and Tirzepatide reduce alcohol consumption in individuals with obesity. Quddos, F., Hubshman, Z., Tegge, A., et al.[2023]

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]

In a network meta-analysis of 26 randomized controlled trials, subcutaneous semaglutide (1 mg once-weekly) significantly reduced HbA1c and fasting blood glucose levels compared to placebo, demonstrating its efficacy in managing type 2 diabetes.

While semaglutide showed comparable safety to placebo, it was associated with higher rates of gastrointestinal adverse events, particularly at doses of 0.8 mg and in comparison to tirzepatide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of type 2 Diabetes Mellitus: A systematic review and network meta-analysis of safety and efficacy outcomes. Zaazouee, MS., Hamdallah, A., Helmy, SK., et al.[2022]

Oral semaglutide significantly reduces HbA1c levels and body weight in patients with type 2 diabetes, showing greater efficacy than placebo and other antidiabetic agents in a review of 11 randomized controlled trials involving 9890 patients.

While oral semaglutide is effective in managing blood glucose and weight, it is associated with increased gastrointestinal side effects like nausea and vomiting, although it has a favorable safety profile regarding severe hypoglycemia and cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral semaglutide for type 2 diabetes: A systematic review and meta-analysis. Avgerinos, I., Michailidis, T., Liakos, A., et al.[2021]

In a one-year study of 35 alcohol-dependent patients, treatment with gamma hydroxybutyrate (GHB) resulted in a 60% completion rate, with 11.4% achieving complete abstinence and 14.3% significantly reducing their alcohol intake.

The study found that administering GHB in six daily doses was a key factor in retaining patients in treatment, as those still in treatment after one year showed significant differences from nonresponders in various clinical measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term therapy using GHB (sodium gamma hydroxybutyrate) for treatment-resistant chronic alcoholics. Maremmani, I., Lamanna, F., Tagliamonte, A.[2015]

In a study of 675 alcohol-dependent patients over 52 weeks, nalmefene (18 mg/day) was found to significantly reduce heavy drinking days and total alcohol consumption compared to placebo, particularly notable at month 13.

While nalmefene showed long-term efficacy and improvements in clinical outcomes, it also had a higher incidence of mild to moderate adverse events, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy, tolerability and safety of nalmefene as-needed in patients with alcohol dependence: A 1-year, randomised controlled study. van den Brink, W., Sørensen, P., Torup, L., et al.[2022]

In a 12-week clinical trial with 150 alcohol-dependent individuals, topiramate significantly improved overall well-being, quality of life, and reduced harmful drinking consequences compared to placebo.

Topiramate not only helped participants drink less but also enhanced their psychosocial functioning, indicating its potential as an effective treatment for alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral topiramate reduces the consequences of drinking and improves the quality of life of alcohol-dependent individuals: a randomized controlled trial. Johnson, BA., Ait-Daoud, N., Akhtar, FZ., et al.[2022]

In a phase IIb trial involving 509 alcohol-dependent patients, sodium oxybate (SMO) did not show significant efficacy in maintaining abstinence for the overall population due to a high placebo response, but it did demonstrate statistically significant improvements in secondary endpoints.

Specifically, severe alcohol-dependent patients showed a meaningful increase in the percentage of days abstinent and overall abstinence rates, suggesting that SMO may be particularly beneficial for those with more severe alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating alcohol dependence with an abuse and misuse deterrent formulation of sodium oxybate: Results of a randomised, double-blind, placebo-controlled study. Guiraud, J., Addolorato, G., Aubin, HJ., et al.[2022]

In a new double-blind, placebo-controlled trial (PREDICT) with 426 alcohol-dependent patients, neither acamprosate nor naltrexone showed additional benefits over placebo in preventing heavy drinking, contrasting with positive results for naltrexone in the earlier COMBINE Study with 459 patients.

The differences in outcomes between the PREDICT and COMBINE studies may be due to variations in treatment settings, suggesting that the environment and patient characteristics can significantly influence the efficacy of alcohol dependence treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a double-blind, placebo-controlled pharmacotherapy trial in alcoholism conducted in Germany and comparison with the US COMBINE study. Mann, K., Lemenager, T., Hoffmann, S., et al.[2018]

References

1. 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]

2. 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]

3. Netherlands pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Does glucagon-like peptide-1 (GLP-1) receptor agonist stimulation reduce alcohol intake in patients with alcohol dependence: study protocol of a randomised, double-blinded, placebo-controlled clinical trial. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Semaglutide and Tirzepatide reduce alcohol consumption in individuals with obesity. [2023]

6. England 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. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of type 2 Diabetes Mellitus: A systematic review and network meta-analysis of safety and efficacy outcomes. [2022]

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

Oral semaglutide for type 2 diabetes: A systematic review and meta-analysis. [2021]

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

Long-term therapy using GHB (sodium gamma hydroxybutyrate) for treatment-resistant chronic alcoholics. [2015]

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

Long-term efficacy, tolerability and safety of nalmefene as-needed in patients with alcohol dependence: A 1-year, randomised controlled study. [2022]

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

Oral topiramate reduces the consequences of drinking and improves the quality of life of alcohol-dependent individuals: a randomized controlled trial. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Treating alcohol dependence with an abuse and misuse deterrent formulation of sodium oxybate: Results of a randomised, double-blind, placebo-controlled study. [2022]

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

Results of a double-blind, placebo-controlled pharmacotherapy trial in alcoholism conducted in Germany and comparison with the US COMBINE study. [2018]