Semaglutide for Tobacco Use

(ONSET Trial)

Overseen By Project Manager

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Oklahoma

Must not be taking: Nicotine replacement, GLP-1 agonists

Disqualifiers: Schizophrenia, Bipolar, Diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests semaglutide to determine if it can help people who smoke and have obesity reduce their tobacco use. Participants will receive either semaglutide or a placebo once a week for 12 weeks. Researchers will examine changes in smoking habits, cravings, and health markers like blood sugar levels. Individuals who smoke more than two cigarettes daily, have obesity, and aren't currently trying to quit smoking might be suitable candidates. As a Phase 4 trial, semaglutide is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

Do I need to stop my current medications to join the trial?

The trial requires that you do not use nicotine replacement therapy or other quit smoking medications, and you must not have used GLP-1 agonists or other weight-lowering or glucose-lowering medications in the past 6 months. If you are on these medications, you would need to stop them to participate.

What is the safety track record for this treatment?

Research has shown that semaglutide is generally well-tolerated and is already approved by the FDA for treating diabetes and aiding weight loss. Users of semaglutide for these conditions have reported mild to moderate side effects, such as nausea, vomiting, and diarrhea, which often decrease over time.

Regarding smoking, semaglutide has been linked to a reduced need for medical care related to tobacco use disorder, suggesting it might be safe for smokers, though specific side effects for this use are not well-documented.

Since this trial is in a later stage, substantial evidence already supports semaglutide's safety in humans. However, as with any treatment, individual reactions can vary, so careful monitoring during the trial remains important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for tobacco use involve nicotine replacement therapies or medications like varenicline and bupropion that work by reducing cravings and withdrawal symptoms. But semaglutide works differently, targeting the body's appetite regulation system. Originally used for diabetes and weight management, semaglutide is a GLP-1 receptor agonist that may help reduce the urge to smoke by influencing the brain's reward system. Researchers are excited because this novel mechanism could offer a fresh approach to smoking cessation, potentially benefiting those who haven't succeeded with traditional methods.

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

Research has shown that semaglutide might help people smoke less. In studies, individuals taking semaglutide visited the doctor less frequently for smoking-related issues. It also appeared to reduce the need for treatments and counseling to quit smoking. Additionally, semaglutide may aid in weight loss, which can be beneficial when trying to quit smoking. This trial will compare semaglutide to a placebo to evaluate its effectiveness in helping people stop smoking, particularly those who are overweight. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adult smokers with obesity (BMI ≥30 kg/m2) aged 18-65 who smoke more than 2 cigarettes per day but don't immediately want to quit. It's not for those with certain medical conditions like thyroid cancer, pancreatitis, diabetes, severe psychiatric issues, or abnormal clinical labs. People on smoking cessation meds or with a history of bariatric surgery are also excluded.

Inclusion Criteria

No immediate desire to quit tobacco use (using criteria from the clinical practice guidelines for treating tobacco dependence)

My BMI is 30 or higher.

Report daily use of >2 cigarettes per day (CPD), as this is a sufficient threshold for detecting tobacco use disorder

Exclusion Criteria

I have a history of specific thyroid cancer, genetic conditions, pancreatitis, diabetes, or related complications.

I do not have severe mental health issues that would stop me from completing the study.

Clinical labs out of range/unacceptable: creatinine ≥ 2 mg/dL, eGFR ≤ 60 mL/min/1.73 m2, triglycerides > 500 mg/dl, ALP > 4x the upper normal limit, abnormal blood lipase levels, other substantially abnormal clinical lab values as determined by the Study Practitioner, A1C 6.5% or higher, Glucose >126 mL fasting or >200mg/dL random, Alanine aminotransferase (ALT) >3x upper normal limit

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 injections once a week for 12 weeks to assess changes in tobacco use and related health biomarkers

12 weeks

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 study tests if Semaglutide can affect tobacco use and health markers in obese smokers over 12 weeks compared to a placebo. Participants will be randomly assigned to either the drug or placebo group and monitored through smartphone surveys and biological assessments including epigenetics and glucose levels via CGM.

How Is the Trial Designed?

Group I: Semaglutide Active Control 1 Intervention

Participants will be randomized to receive active semaglutide or placebo (saline) injection once a week for 12weeks

Group II: Placebo Placebo Group 1 Intervention

Participants will be randomized to receive active semaglutide or placebo (saline) injection once a week for 12weeks

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Citations

1. 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 ...

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

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 a ...

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. 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.

5. healio.com healio.com/news/primary-care/20240801/semaglutide-shows-potential-as-smoking-cessation-tool

Semaglutide shows potential as smoking cessation tool In every comparison, results showed an association between semaglutide and fewer tobacco use disorder-related health care encounters.

6. uspharmacist.com uspharmacist.com/article/semaglutide-associated-with-reduced-tobacco-use-disorder-risk

Semaglutide Associated With Reduced Tobacco Use ... New use of semaglutide was associated with a lower risk for medical care related to tobacco use disorder (TUD) in smokers with type 2 diabetes mellitus (T2DM), ...