Tirzepatide to be evaluated in multi-site trial for smoking cessation and post-cessation weight gain.
Background
Cigarette smoking remains a leading cause of preventable morbidity and mortality, often complicated by post-cessation weight gain, which can deter cessation efforts. Current smoking cessation aids have varying efficacy, and new strategies are needed, particularly for individuals with overweight or obesity who face higher health risks. GLP-1 receptor agonists (GLP-1RAs) like tirzepatide, known for their effects on glucose metabolism and weight loss, are also being investigated for neuropsychiatric conditions, including substance use disorders, suggesting a potential role in addiction treatment. This trial addresses the gap in effective cessation strategies that also mitigate weight gain.
Study Design
This multi-site, parallel-arm, dose-escalating, placebo-controlled trial plans to recruit 300 treatment-seeking people who smoke (PWS) with a body mass index of 25 kg/m2 or greater. Participants will be randomized to receive subcutaneous tirzepatide or placebo weekly over 16 weeks, with follow-up at Week 17 and Week 27. The medication will follow a standard dose titration schedule, starting at 2.5mg/week and escalating to a final dose of 10mg/week. All participants will also receive nicotine patches as a co-intervention. The study will be conducted across four academic sites.
Results
This multi-site clinical trial is designed to generate data on the efficacy of tirzepatide for smoking cessation and associated outcomes. The primary endpoint will be smoking cessation rates, likely measured by sustained abstinence. Secondary outcomes are expected to include the mitigation of post-cessation weight gain, a common barrier to successful quitting. The trial will also assess the safety and tolerability profile of tirzepatide in this specific population. While no results are available yet, the study aims to determine if tirzepatide can significantly improve cessation outcomes compared to placebo, especially in individuals with overweight or obesity.
Why It Matters
If successful, this trial could establish tirzepatide as a novel, dual-action therapeutic for smoking cessation, particularly beneficial for people who smoke with overweight or obesity. This could offer a significant advantage over existing cessation aids by simultaneously addressing post-cessation weight gain, a major deterrent to quitting. The detailed dose titration schedule (2.5mg/week to 10mg/week) outlined in the protocol provides a clear framework for potential clinical translation. Clinicians could eventually prescribe tirzepatide to help patients quit smoking while managing weight, potentially improving long-term health outcomes and adherence to cessation programs. This research moves beyond current GLP-1RA applications, exploring new therapeutic avenues for addiction.