CompletedPhase 2Results posted

Effects of Semaglutide on Nicotine Intake

Effects of Semaglutide on Nicotine Intake and Smoking Lapse

Lead sponsor

University of North Carolina, Chapel Hill

Asset

Semaglutide

Subcutaneous · GLP-1 agonist

Listed sites

Recruiting sites

Actual enrollment

Study population

Alcohol / substance use

Eligibility highlights

Primary endpoints

•Alcohol consumption, change•Nicotine Reinstatement Duration

Registered trial locations

Locations reported to ClinicalTrials.gov for this trial snapshot. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT05530577

Org study ID21-1548

Secondary IDR21DA047663-02

Timeline

Milestones

Study first posted2022-09-07actual

Study start2022-10-07actual

Primary completion2024-05-13actual

Study completion2024-05-13actual

Results first posted2025-07-18actual

Last update posted2025-08-22actual

Assets

Investigational agents

Semaglutide

Who this study enrolls

Alcohol / substance use

Who can enroll

Minimum age21 Years

Maximum age65 Years

SexAll

Healthy volunteersAccepted

Inclusion criteria

•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

Exclusion criteria

•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

•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:

1. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)

2. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)

3. intrauterine device

4. intrauterine hormone-releasing system

5. bilateral tubal occlusion

6. vasectomized partner

7. 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)

Endpoints (14)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other clinical outcomes

Weight & body composition

Glycemic / diabetes

Weight & body composition

2 endpoints

Other/protocol endpoint

Change in Body Weight

Time frame:baseline (Week 0) to study endpoint (Week 10)

Body weight, absolute change (kg)

change from baseline, improvement

Other_pre_specified/registry result

Change in Body Weight

Time frame:baseline (Week 0) to study endpoint (Week 10)

Body weight, absolute change (kg)

change from baseline, improvement

Glycemic / diabetes

2 endpoints

Other/protocol endpoint

Change in HbA1c

Time frame:baseline (Week 0) to study endpoint (Week 10)

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Other_pre_specified/registry result

Change in HbA1c

Time frame:baseline (Week 0) to study endpoint (Week 10)

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Other clinical outcomes

10 endpoints

Primary/registry result/low confidence

Change in Nicotine Self-Administration

Time frame:Baseline (Week 0) to post-medication (Week 8)

Alcohol consumption, change

change from baseline, improvement

Posted result

Group	Mean · Number of cigarettes	95% CI
Semaglutide	-0.8	-
Sham/Placebo	-0.5	-

Primary/registry result

Change in Nicotine Reinstatement Duration

Time frame:Baseline (Week 0) to post-medication (Week 8)

change from baseline, improvement

Posted result

Group	Mean · Minutes	95% CI
Semaglutide	10.3	-
Sham/Placebo	-2.2	-

Primary/protocol endpoint/low confidence

Change in Nicotine Self-Administration

Time frame:Baseline (Week 0) to post-medication (Week 8)

Alcohol consumption, change

change from baseline, improvement

Primary/protocol endpoint

Change in Nicotine Reinstatement Duration

Time frame:Baseline (Week 0) to post-medication (Week 8)

change from baseline, improvement

Secondary/registry result/low confidence

Change in Daily Cigarette Smoking

Time frame:Baseline (Week 0) to study endpoint (Week 10)

change from baseline, improvement

Posted result

Group	Mean · Number of cigarettes per day	95% CI
Semaglutide	-3.35	-
Sham/Placebo	-2.27	-

Secondary/protocol endpoint/low confidence

Change in Daily Cigarette Smoking

Time frame:Baseline (Week 0) to study endpoint (Week 10)

Alcohol consumption, change

change from baseline, improvement

Other/protocol endpoint

Change in Cigarette Craving

Time frame:baseline (Week 0) to post-medication (Week 8)

change from baseline, improvement

Other/protocol endpoint

Change in Subjective Responses to Cigarette Smoking

Time frame:baseline (Week 0) to post-medication (Week 8)

change from baseline, improvement

Other_pre_specified/registry result/low confidence

Change in Cigarette Craving

Time frame:baseline (Week 0) to post-medication (Week 8)

change from baseline, improvement

Other_pre_specified/registry result

Change in Subjective Responses to Cigarette Smoking

Time frame:baseline (Week 0) to post-medication (Week 8)

change from baseline, improvement

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

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.
PMID42189538via clinicaltrials gov reference derived

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 6, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 6, 2026 snapshot.