Semaglutide for Nicotine Addiction

Overseen By Margret Powell

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Nicotine replacement, Insulin, Weight control

Disqualifiers: Severe mental illness, Diabetes, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: Unknown

Duration: 9 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore whether semaglutide, a medication typically used for diabetes, can help people quit smoking by reducing nicotine cravings and consumption. Researchers are investigating if this drug, which affects certain brain receptors, can change smoking behaviors. Participants will receive either semaglutide or a placebo (a substance with no active ingredients) for comparison. The trial seeks individuals who smoke at least 5 cigarettes a day and have struggled to quit smoking for over a year. 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 have not used certain medications like nicotine replacement therapies, semaglutide, or other GLP-1 agonists in the past 30 days. If you are currently using medications that may interact with semaglutide, you may need to stop taking them to participate.

Is there any evidence suggesting that semaglutide is likely to be safe for humans?

Research shows that semaglutide is generally well-tolerated. It has primarily been used for weight loss and diabetes, but researchers are now exploring its potential to help people quit smoking. The FDA has approved semaglutide for other uses, indicating that its safety is well understood.

The most common side effects include nausea and mild stomach issues, which typically improve over time. Studies for its approved uses have reported no major safety concerns. Therefore, while semaglutide is being tested for aiding nicotine addiction, previous research and use support its overall safety in humans. ^{1 2 3 4 5}

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

Unlike current treatments for nicotine addiction, which often include nicotine replacement therapies and medications like varenicline or bupropion, semaglutide offers a novel approach. Semaglutide is unique because it is a glucagon-like peptide-1 (GLP-1) receptor agonist, typically used for diabetes and weight management, which may affect the brain's reward pathways involved in nicotine dependence. Researchers are excited about semaglutide because it targets these pathways differently, potentially reducing cravings and withdrawal symptoms more effectively than traditional methods. Additionally, the treatment is administered through subcutaneous injections, providing a controlled and gradual release that could enhance its effectiveness in tackling addiction.

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

Research suggests that semaglutide, a treatment under study in this trial, might help people quit smoking. Studies have found that individuals using semaglutide required fewer prescriptions for other smoking cessation aids and counseling. Similar results appeared with another medication, exenatide, which helped people stop smoking and reduced their cravings. These early findings indicate that semaglutide could aid smoking cessation by altering the body's response to nicotine. While more research is needed, these results offer hope for its potential use in treatments to help people stop smoking. ^{1 2 3 6 7}

Who Is on the Research Team?

Christian Hendershot, PhD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

This trial is for adults aged 21-65 who smoke at least 5 cigarettes daily over the past year without a break of more than 90 days. Participants must have moderate nicotine dependence, be motivated to quit within the next 3-18 months, and willing to take study medication and attend lab sessions involving smoking. Exclusions include those with diabetes, certain medical conditions or histories (like cancer), uncontrolled blood pressure, extreme BMI values, use of conflicting medications or substances, and women who are pregnant or not using effective contraception.

Inclusion Criteria

Willingness to take study medication and complete study procedures

I am between 21 and 65 years old.

Willingness to complete lab sessions involving cigarette smoking

Exclusion Criteria

I have used vaping products, cigars, chewing tobacco, or snuff at least once a week in the last month.

I have had diabetic ketoacidosis in the past.

I have diabetes or my HbA1c level was over 6.5% at screening.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive semaglutide or placebo via subcutaneous injections over 9 weeks

9 weeks

Weekly visits for injections

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Semaglutide

Trial Overview The trial tests Semaglutide's effects on nicotine intake among smokers. It's a double-blind study where participants won't know if they're getting Semaglutide or a placebo. The goal is to see if this drug can help reduce cigarette consumption by affecting biological mechanisms related to addiction.

How Is the Trial Designed?

Group I: Semaglutide Experimental Treatment 1 Intervention

Participants will receive semaglutide via subcutaneous injections at escalating doses (0.25mg to 1.0mg) over 9 weeks.

Group II: Sham/Placebo Placebo Group 1 Intervention

Participants will receive sham subcutaneous injections over 9 weeks.

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

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 (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]

Subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to provide superior and sustained glycemic control and weight loss in over 8000 patients with type 2 diabetes, as demonstrated in the SUSTAIN clinical trial program.

In the SUSTAIN 6 trial, semaglutide significantly reduced the risk of cardiovascular events in patients at high risk, indicating its cardiovascular safety and efficacy compared to placebo and standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials. Aroda, VR., Ahmann, A., Cariou, B., et al.[2020]

Semaglutide (Ozempic®) is a new subcutaneous treatment for type 2 diabetes that effectively lowers blood glucose levels by stimulating insulin release and also helps reduce body weight.

The once-weekly injection has been approved in the US, Puerto Rico, and Canada, and is also under review in other countries, with ongoing clinical development for additional conditions like obesity and liver diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide: First Global Approval. Dhillon, S.[2019]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11128349/

Targeting GLP-1 receptors to reduce nicotine use disorder Specifically, after six weeks of treatment 46.3 % of participants receiving exenatide + NRT were abstinent compared to 26.8 % of participants treated with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39074369/

Association of Semaglutide With Tobacco Use Disorder in ... Semaglutide was associated with reduced smoking cessation medication prescriptions and counseling. Similar findings were observed in patients with and without ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1551714425001831

A randomized controlled trial of once-weekly semaglutide ... We anticipate that semaglutide 2.4 mg once-weekly will provide a clinically meaningful effect on weight management in the context of smoking cessation.

4. ddw-online.com ddw-online.com/semaglutide-ozempic-found-to-treat-smoking-addiction-30924-202407/

Semaglutide (Ozempic) found to treat smoking addiction In a 2021 study in Texas, US, exenatide, another GLP-1 receptor agonist, was proved to improve smoking abstinence, reduce craving and withdrawal ...

5. acpjournals.org acpjournals.org/doi/10.7326/M23-2718

Association of Semaglutide With Tobacco Use Disorder in ... Semaglutide was associated with a lower risk for smoking cessation counseling compared with other antidiabetes medications with HRs ranging from 0.69 to 0.85, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05530577

NCT05530577 | Effects of Semaglutide on Nicotine Intake This study will provide initial laboratory evidence for the potential efficacy of GLP-1 receptor agonists as adjunctive treatments for smoking cessation.

7. nature.com nature.com/articles/s41380-024-02498-5

Association of semaglutide with reduced incidence and ... In summary, our results show that semaglutide was associated with a lower risk for both incident and relapse of CUD compared to non-GLP-1 RA ...