7625 Functional and structural neuronal changes of dulaglutide compared to placebo during smoking cessation - a randomized placebo-controlled trial

Abstract Disclosure: C.O. Sailer: None. S. Lengsfeld: None. D. Coynel: None. F. Baur: None. K. Bologna: None. T. Vukajlovic: None. N.A. Jeanloz: None. C. Bathelt: None. D. Zanchi: None. M. Christ-Crain: None. B.F. Winzeler: None. Introduction: Nicotine activates reward-related brain regions and chronic cigarette smoking can lead to functional and structural neuronal changes. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), known for their anti-obesity effects, have emerged as potential treatments for addictive disorders. A pilot study of exenatide vs placebo revealed increased short-term smoking abstinence rates and reduce smoking craving. We previously reported the results of a clinical trial (n=255) investigating the effect of dulaglutide vs placebo on smoking cessation. Herein, we report the functional magnetic resonance imaging (fMRI) results of a subset of participants. This substudy aimed to investigate the influence of dulaglutide on smoking craving, functional and structural neuronal changes of smokers aiming to quit smoking. Methods: This single-center, randomized, double-blind, placebo-controlled trial enrolled 71 participants with at least a moderate nicotine dependence, all committed to quitting smoking. Of these, 35 participants received 12 weeks dulaglutide 1.5mg, and 36 participants placebo, alongside varenicline treatment and behavioral counselling. An fMRI session was conducted at baseline and 12 weeks. The primary outcomes included smoking craving assessed on a visual analogue scale (VAS, range 0-7), differences in blood oxygen level dependent (BOLD) signal (whole brain and regions of interests, e.g., nucleus accumbens, amygdala, thalamus) and gray matter changes between sessions and groups when exposed to smoking and neutral video cues. Secondary outcomes assessed the above in quitters vs persistent smokers. Results: In line with the primary study findings, abstinence rates at 12 weeks were comparable in the dulaglutide (54%) and placebo (68%) groups (p=0.27). In a mixed effect model, smoking craving significantly decreased at 12 weeks vs baseline (-2.13 (95% CI -2.46, -1.80), p