Semaglutide for Alcoholism

Overseen By Lorenzo Leggio, M.D.

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

Trial Summary

What is the purpose of this trial?

Background: Alcohol use disorder (AUD) is a problematic pattern of alcohol use accompanied by clinically significant medical consequences. Medications can help most people reduce their drinking, but the number is limited, and additional treatment options are needed. Objective: To test if a medication named Semaglutide is safe and may reduce alcohol drinking in people with AUD. Who can participate? All Adults aged 18 or older with AUD might be eligible to participate in the study. What will happen during the study? Participants will visit the National Institute on Drug Abuse (NIDA) in Baltimore once a week for about 20 weeks (5 months). Each visit will last between 2 and 6 hours depending on the tasks scheduled for that visit. Participants will be assigned by chance (like flipping a coin) to receive either Semaglutide or placebo. A placebo looks just like a real drug but contains no medicine. The study medication is given as a shot under the skin each week. Participants will undergo different tests throughout the study: They will give blood, urine, and saliva samples. They will engage in self-paced behavioral therapy on a computer. They will answer questions about their mood, diet, alcohol drinking and craving, tobacco use, etc. They will taste several sweet liquids and tell their preferences. They will sit in a bar-like room and be exposed to cues that might make them feel the urge to eat food or drink alcohol. They will wear a virtual reality headset that creates a cafeteria setting. They will walk the virtual cafeteria and choose food and drinks from a buffet. They will have a functional magnetic resonance imaging (fMRI) scan to take pictures of their brain. During the scans, participants will be shown pictures of alcohol-containing drinks, food, and other items.They will perform tasks on a computer screen. Participants will have a follow-up visit about 7 weeks after their last shot.

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.

What data supports the effectiveness of the drug Semaglutide for treating alcoholism?

Semaglutide, a drug used for type 2 diabetes, has shown effectiveness in controlling blood sugar levels and promoting weight loss. While it is not directly studied for alcoholism, its ability to influence weight and metabolism might suggest potential benefits in managing alcohol-related health issues. ^{1 2 3 4 5}

Is semaglutide safe for humans?

Semaglutide, used under names like Rybelsus and Ozempic, has been tested in people with type 2 diabetes and shown to be generally safe. It has a safety profile similar to other drugs in its class and does not increase heart-related risks compared to a placebo. ^{1 2 3 5 6}

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

Semaglutide is unique because it is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) originally used for type 2 diabetes, which may help with weight loss and potentially reduce alcohol cravings. Unlike traditional alcoholism treatments, it is administered once weekly as an injection or taken orally, offering a novel approach by targeting metabolic pathways. ^{1 2 3 4 7}

Research Team

Lorenzo Leggio, M.D.

Principal Investigator

National Institute on Drug Abuse (NIDA)

Eligibility Criteria

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 am 18 years old or older.

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

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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, 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]

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]

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]

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]

References

1. Belgium pubmed.ncbi.nlm.nih.gov

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

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

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

3. Japan pubmed.ncbi.nlm.nih.gov

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

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

Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials. [2022]

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

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. [2022]

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. England pubmed.ncbi.nlm.nih.gov

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