AzTrials
AzTrials

Tobacco Use DisorderPhase 2NCT05530577

Effects of Semaglutide on Nicotine Intake

A Phase 2 study testing Semaglutide in people with Tobacco Use Disorder and Nicotine Addiction, run by University of North Carolina, Chapel Hill at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Tobacco use remains the foremost cause of preventable deaths in the U.S. and worldwide. Advancing new smoking cessation therapies, including those targeting novel biological mechanisms, is a critical public health priority. Read more about this study

Who is it for?
Ages 21 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Tobacco Use Disorder, Nicotine Addiction
What is being tested?
Semaglutide
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
24 participants
Where
1 siteUnited States
Study dates
7 Oct 2022to 13 May 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Age 21-65
  • Smoking 5+ cigarettes per day (on average) over the past year, with no period of abstinence > 90 days
  • Biochemical verification of smoking status, based on expired CO > 8 at baseline
  • Willingness to take study medication and complete study procedures
  • Willingness to complete lab sessions involving cigarette smoking
  • Ability to communicate in English

Who cannot join

  • Regular use of electronic nicotine delivery systems (ENDS/vaping), cigars, chewing tobacco or snuff, based on at least weekly use in the past 30 days
  • Past 30-day use of nicotine replacement therapies/products
  • Reporting past 30-day use of illicit drugs other than cannabis at baseline, or having a positive toxicology screen for illicit drugs other than cannabis at baseline
  • Current engagement in alcohol or smoking cessation treatments, or currently engaged in intentional efforts to quit cigarette use
  • Past 30-day use of: Sincalide, Sulfonylureas, insulin and insulin products or other medications that may interact with semaglutide, or weight control medications
  • Prior use of semaglutide or other GLP-1 agonists
Show all 31Show fewer
  • Known or suspected hypersensitivity to study medication or related products
  • Lifetime diagnosis of severe mental illness (including schizophrenia and bipolar disorder)
  • Meeting criteria for current alcohol use disorder (AUD) or other substance use disorder (with the exception of tobacco or mild cannabis use disorder)
  • History of suicide attempt, or recent (past 30 day) suicidal ideation, or psychiatric hospitalization in the last 6 months
  • Current significant medical or neurological illness (based on self-report or medical record) including severe hepatic impairment or cirrhosis, impaired renal function (eGFR <50ml/min), acute or chronic pancreatitis, gastroparesis, gallbladder disease or cholelithiasis, other severe gastrointestinal disease, heart failure, coronary artery disease, stroke, seizure disorder, or other medical condition that poses a risk for the medication or alcohol administration components of the study (as determined by the MD)
  • A personal or family history of medullary thyroid cancer or multiple endocrine neoplasia 2A or 2B
  • Calcitonin greater than or equal to 50 ng/L
  • Uncontrolled thyroid disease at screening
  • History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g., subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)
  • History of Type 1 or Type 2 diabetes, or HbA1c >6.5% measured at screening
  • History of diabetic retinopathy, proliferative retinopathy, or maculopathy
  • History of diabetic ketoacidosis
  • History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ)
  • Currently nursing, pregnant, anticipating pregnancy in the next 6 months, or not using a highly effective contraceptive method as judged by the MD, and defined as:
  • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
  • progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
  • intrauterine device
  • intrauterine hormone-releasing system
  • bilateral tubal occlusion
  • vasectomized partner
  • sexual abstinence
  • Elevation of serum lipase, amylase, direct (conjugated) bilirubin, or alkaline phosphatase (ALP), ALT, or AST) more than 3X the upper limit of normal on baseline bloodwork
  • Baseline body mass index (BMI) <23kg/m^2
  • Uncontrolled hypertension or systolic BP >180 mmHg and/or diastolic BP >105 mmHg, averaged from three measurements
  • Plans for travel outside of the local area in the upcoming 12 weeks that would interfere with lab visits during the study period (or other logistic factors that would make it difficult to commit to entire duration of study)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

Other trials in United States

About this study

Official title: Effects of Semaglutide on Nicotine Intake and Smoking Lapse

Tobacco use remains the foremost cause of preventable deaths in the U.S. and worldwide. Advancing new smoking cessation therapies, including those targeting novel biological mechanisms, is a critical public health priority. Accumulating evidence from preclinical studies suggests that glucagon-like peptide-1 (GLP-1) receptor agonists reduce intake and/or reinstatement of addictive drugs, including nicotine. However, translational work is necessary to establish whether GLP-1 receptor agonists alter aspects of nicotine response and smoking behavior in smokers. Human laboratory studies play a pivotal role in drug development by providing a time- and cost-efficient means of validating preclinical findings, also providing an ideal platform for studying mechanisms of medication effects. This is an experimental investigation to examine the effects of an approved GLP-1 receptor agonist on nicotine intake and reinstatement. Dependent smokers will be enrolled in a double-blind, parallel-arm trial with laboratory endpoints. Laboratory procedures will include a validated procedure for measuring smoking lapse/reinstatement after overnight abstinence. This study will provide initial laboratory evidence for the potential efficacy of GLP-1 receptor agonists as adjunctive treatments for smoking cessation.

Being tested
Semaglutide, Sham/placebo
Medical subject headings
Tobacco Use Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SemaglutideDrug

    Semaglutide (subcutaneous)

  • Sham/placeboDrug

    Sham subcutaneous injection

Study groups in NCT05530577
Study groupRoleWhat they receive
SemaglutideExperimentalParticipants will receive semaglutide via subcutaneous injections at escalating doses (0.25mg to 1.0mg) over 9 weeks.
Receives: Drug: Semaglutide
Sham/PlaceboSham comparatorParticipants will receive sham subcutaneous injections over 9 weeks.
Receives: Drug: Sham/placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Nicotine Self-Administration

    Number of cigarettes smoked during a laboratory smoking procedure

    Measured: Baseline (Week 0) to post-medication (Week 8)

  2. Change in Nicotine Reinstatement Duration

    Duration (minutes) of resistance to smoking reinstatement during a laboratory lapse task

    Measured: Baseline (Week 0) to post-medication (Week 8)

Secondary outcomes (1)

  1. Change in Daily Cigarette Smoking

    Number of cigarettes consumed per day during medication exposure

    Measured: Baseline (Week 0) to study endpoint (Week 10)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Sep 2022
  2. Study start7 Oct 2022
  3. Primary completion13 May 2024
  4. Study completion13 May 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized parallel group design.
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05530577
Sponsor's protocol ID
21-1548
Other IDs
R21DA047663-02
Status last verified
Jul 2024
First submitted
26 Aug 2022
Last updated
22 Aug 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD will be shared with other investigators upon reasonable request.

Publications

  • Hendershot CS, Bremmer MP, Paladino MB, Kostantinis G, Gilmore TA, Sullivan NR, Tow AC, Prince MA, Dermody SS, Jordan R, McKee SA, Fletcher PJ, Claus ED, Klein KR. Once-Weekly Semaglutide in Adults With Daily Cigarette Use: A Randomized Clinical Trial. JAMA Netw Open. 2026 May 1;9(5):e2614898. doi: 10.1001/jamanetworkopen.2026.14898.

    PubMed 42189538

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Semaglutide in people with Tobacco Use Disorder and Nicotine Addiction, run by University of North Carolina, Chapel Hill at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Nicotine Self-Administration (time frame: Baseline (Week 0) to post-medication (Week 8)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05530577, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in