Effect of glucagon-like peptide-1 receptor agonists on cigarette smoking consumption in type 2 diabetes patients: study protocol of a randomized, parallel -controlled clinical trial

Introduction Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type 2 diabetes mellitus (T2DM) and may influence reward-related pathways, suggesting potential effects on nicotine dependence and smoking-related outcomes. Randomized evidence in patients with T2DM remains limited. This trial evaluates the effects of GLP-1RAs on nicotine dependence and smoking exposure and explores potential neural mechanisms using functional MRI (fMRI). Methods and analysis This single-center, parallel-group randomized controlled trial will enroll 46 male adults with T2DM who are current smokers with Fagerström Test for Nicotine Dependence (FTND) score ≥4. Participants will be randomized (1:1) to receive a GLP-1RA or a dipeptidyl peptidase-4 inhibitor (DPP-4i) for 24 weeks as part of routine glucose-lowering therapy optimization. No structured smoking cessation counseling or smoking cessation pharmacotherapy will be provided by the research team. The primary endpoint is change in FTND score from baseline, assessed at weeks 1, 4, 8, 12, and 24. Secondary endpoints include changes in exhaled carbon monoxide (CO) and smoking cessation rate at weeks 12 and 24, and changes in metabolic parameters. Exploratory endpoints include changes in resting-state fMRI measures from baseline to week 24 and their associations with smoking- and metabolic-related outcomes. Trial status Recruitment started in June 2025 and is ongoing. Clinical Trial Registration ClinicalTrials.gov , identifier (NCT06924697).