Multi-Site Trial of Tirzepatide for Smoking Cessation

NCT07602699 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: HS-25-00642U01DA064384
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 4

Brief Summary

This multi-site clinical trial will generate data on the efficacy of tirzepatide for smoking cessation and associated outcomes (e.g., post-cessation weight gain) in treatment-seeking people who smoke (PWS) with overweight or obesity. A sample of 300 treatment-seeking people who smoke with body mass index of 25 kg/m2 or greater will be recruited from four geographic sites (University of Southern California, Yale University, University of Chicago, and University of Colorado Anschutz Medical Campus) to participate in a parallel-arm, dose-escalating, placebo-controlled trial. Participants will attend weekly clinic visits to receive subcutaneous tirzepatide or placebo over 16 weeks (Visit Weeks 1-16), followed by follow-up visits at Week 17 and Week 27. Medication will be prescribed according to the standard dose titration schedule for the first 16 weeks of treatment (initial dose: 2.5mg/week; final dose: 10mg/week). All participants will also receive nicotine patches.

Conditions

Smoking Cessation; Smoking Behaviors

Keywords

Addiction; GLP-1; Tirzepatide; Substance Use Disorder

Outcome Measures

Primary Outcomes (1)

• 7-day point prevalence abstinence

  Biochemically verified abstinence from cigarette smoking

  From baseline through 16 weeks of treatment (final assessment at Week 17 visit) and at 6 months after the target quit date (assessed at Week 27 visit)

Secondary Outcomes (2)

• Cigarettes per day

  From baseline through 16 weeks of treatment (final assessment at Week 17 visit)

• Weekly cigarette craving

  Baseline through 16 weeks of treatment (final assessment at Week 17 visit)

Other Outcomes (3)

• Current cigarette craving

  Baseline through 16 weeks of treatment (final assessment at Week 17 visit)

• Smoking withdrawal

  Baseline through 16 weeks of treatment (final assessment at Week 17 visit)

• Body weight

  Treatment week 1 through treatment week 16 (final assessment at Week 17 visit)

Study Arms (2)

Tirzepatide

EXPERIMENTAL

Drug: Tirzepatide

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Tirzepatide DRUG

Participants will receive tirzepatide (subcutaneous injection) at doses of 2.5mg for Weeks 1-4, 5mg for Weeks 5-8, 7.5mg for Weeks 9-12, and 10mg for Weeks 13-16

Tirzepatide

Placebo OTHER

Participants will receive placebo (saline) injections for Weeks 1-16

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 21-65 years
• Body mass index ≥ 25kg/m2 at the baseline screening
• Reporting ≥10 cigarettes per day, on average, for the past 6 months and \> 2 year duration of smoking
• Interest in making a long-term cessation attempt within the next 30-60 days
• Willingness to receive study medication and standard-of-care smoking cessation supports (nicotine replacement therapy and a smoking cessation app)
• Ability to adhere to weekly visits and study procedures over the study period (i.e., no plans to move or travel for extended periods)
• Exhaled CO of \>5ppm at baseline
• Use of an acceptable birth control method for female participants\*
• Ability to read and communicate in English

You may not qualify if:

• BMI \< 25 kg/m2 at screening
• History of diabetes, diabetes-attributable medical conditions, or HbA1c ≥6.5% at baseline
• Recent (past 90 days) active suicidal ideation or lifetime history of suicide attempt
• Current treatment for psychotic disorders or mood disorders with psychotic features (e.g., schizophrenia, schizoaffective disorder, depression with psychotic features), current treatment for bipolar disorder (with or without psychotic features), or current secondary psychosis due to substance use or another medical condition
• Meeting DSM-5 criteria for a current (past 12 months) substance use disorder other than tobacco use disorder, mild or moderate cannabis use disorder, or mild or moderate alcohol use disorder.
• Recent (past 30 day) self-report of illicit drug use (excluding cannabis) or non-prescribed opioids; or positive urine screen for illicit drugs. A positive screen for opioids will be allowed if the participant is prescribed an opioid replacement therapy medication and can provide documentation.
• Past 30-day initiation of psychiatric medications (e.g., SSRIs) or changes to medication dose
• Treatment with tirzepatide or another GLP-1RA medication in the prior 6 months
• Current (past month) treatment with other weight loss, diabetes, or smoking cessation medications (varenicline or bupropion; excluding nicotine replacement products)
• Severe GI disease (e.g., gastroparesis, ulcerative colitis).
• History of gastric bypass surgery or other surgeries of the stomach
• Any health condition or treatment/medication that would preclude the use of tirzepatide or NRT, in the opinion of the study physician, including severe cardiovascular disease
• History of chronic pancreatitis or acute pancreatitis in the last 6 months
• Currently nursing, pregnant, or anticipating pregnancy
• History of diabetic retinopathy, proliferative retinopathy, or maculopathy

Sponsors & Collaborators

• University of Southern California: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (4)

Keck School of Medicine, University of Southern California

Los Angeles, California, 90033, United States

RECRUITING

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

NOT YET RECRUITING

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

NOT YET RECRUITING

University of Chicago Pritzker School of Medicine

Chicago, Illinois, 60637, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Smoking Cessation; Smoking; Behavior, Addictive; Substance-Related Disorders

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Health Behavior; Behavior; Compulsive Behavior; Impulsive Behavior; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Design

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

Study Record Dates

• First Submitted: May 11, 2026
• First Posted: May 22, 2026
• Study Start (Estimated): May 31, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: The protocol and SAP will be made available at or before the completion of the study. Requests for IPD will be reviewed following publication of primary study results.
• Access Criteria: Data will be made available to researchers whose proposed purpose for accessing the data has been approved, and provided a data sharing agreement is in place.

Locations

US (4)