Effects of Semaglutide on Nicotine Intake

NCT05530577 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 21-1548R21DA047663-02
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Tobacco Use Disorder; Nicotine Addiction

Outcome Measures

Primary Outcomes (2)

• Change in Nicotine Self-Administration

  Number of cigarettes smoked during a laboratory smoking procedure

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

• Change in Nicotine Reinstatement Duration

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

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

Secondary Outcomes (1)

• Change in Daily Cigarette Smoking

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

Other Outcomes (4)

• Change in Cigarette Craving

  baseline (Week 0) to post-medication (Week 8)

• Change in Subjective Responses to Cigarette Smoking

  baseline (Week 0) to post-medication (Week 8)

• Change in Body Weight

  baseline (Week 0) to study endpoint (Week 10)

Study Arms (2)

Semaglutide

EXPERIMENTAL

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

Drug: Semaglutide

Sham/Placebo

SHAM COMPARATOR

Participants will receive sham subcutaneous injections over 9 weeks.

Drug: Sham/placebo

Interventions

Semaglutide DRUG

Semaglutide (subcutaneous)

Semaglutide

Sham/placebo DRUG

Sham subcutaneous injection

Sham/Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Results Point of Contact

• Title: Christian Hendershot, PhD
• Organization: University of Southern California

christian.hendershot@usc.edu

323-442-1082

Study Officials

• Christian Hendershot, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized parallel group design.

Study Record Dates

• First Submitted: August 26, 2022
• First Posted: September 7, 2022
• Study Start: October 7, 2022
• Primary Completion: May 13, 2024
• Study Completion: May 13, 2024
• Last Updated: August 22, 2025
• Results First Posted: July 18, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will become available following publication of study manuscripts and will be available indefinitely.
• Access Criteria: Reasonable request from qualified investigator.

Locations

US (1)