You may be eligible for this study if you meet the following criteria.

Qualified participants:

• Ages 21–65
• Looking to quit smoking cigarettes
• Overweight or having obesity (BMI ≥ 25)
• Willing to attend weekly clinic visits and take study medication (tirzepatide or placebo)

Not eligible if you:

• Have a history of diabetes or HbA1c ≥ 6.5%
• Are currently using illicit drugs (excluding cannabis in limited cases)
• Are currently taking certain weight loss, diabetes, or smoking cessation medications (other than nicotine replacement therapy)
• Have recent or active serious psychiatric conditions (such as psychosis or recent suicidal ideation)
• Have medical conditions that would prevent safe use of the study medication, as determined by study staff

Overall Duration

• This study lasts about 27 weeks (a little over 6 months). Participants will attend regular clinic visits throughout the study, with weekly visits during the first 16 weeks, followed by several follow-up visits over the next 11 weeks.

In-Lab Activities

• Participants will complete a screening visit first to see if they qualify, including health questions, basic measurements (such as height, weight, and vital signs), and smoking-related assessments (such as breath carbon monoxide testing). If eligible, participants will be randomly assigned to receive either tirzepatide or a placebo and will attend weekly clinic visits for 16 weeks to receive study medication by injection.
• During visits, participants may also complete questionnaires about smoking habits, mood, and health, as well as brief interviews with study staff. Blood samples and other safety lab tests may be collected to monitor health throughout the study. Some information collected during visits may be recorded by study staff for research purposes.
• After the treatment period, participants will return for follow-up visits at Weeks 17, 21, and 27 to check smoking status, health, and overall progress.

At-Home Activities

• Between visits, participants may be asked to track smoking behavior and complete short surveys about cravings, mood, and cigarette use. These may be done on paper, online, or through a study-provided system depending on site procedures. Participants are encouraged to follow study instructions closely, including any smoking cessation supports provided, such as nicotine replacement therapy and brief counseling.

All responses are kept confidential and are used only for research purposes.

Participants in this study may receive compensation for their time. The exact amount depends on which study visits and activities are completed, and may total up to $1,875 for full participation. Transportation support or reimbursement may also be available depending on the study site. All study-related medication, clinic visits, and smoking cessation support are provided at no cost to participants.

Participants will also receive standard smoking cessation support, which may include nicotine replacement therapy and brief counseling from the study team. In addition, participants may benefit from regular health monitoring, including check-ins on weight, smoking habits, and overall health throughout the study.

There is no cost for you to participate in our research study.