RecruitingPhase 2Drug trialMulti-Site Trial of Tirzepatide for Smoking CessationThis 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.