Endocrine Abstracts

Introduction: Smoking harms women more than men and women seem to be less successful in quitting. Greater concerns about post-cessational weight in women and gender differences in craving and reward processing have been postulated as possible explanations. Our group recently showed that the GLP-1 analogue dulaglutide reduces post-cessational weight gain. We hypothesize that women compared to men might profit more from the weight-lowering effects of dulaglutide in terms of abstinence rates.

Methods: This is a predefined secondary analysis of a placebo-controlled, double-blind, single-center randomized trial including 255 daily smokers (155 women, 100 men). Participants received weekly dulaglutide (1.5mg) or placebo (0.9% sodium chloride) subcutaneous injections for 12 weeks in addition to standardized smoking cessation care. Smoking status was self-reported and confirmed by end-expiratory carbon monoxide measurement. We analyzed gender differences after 12 weeks of dulaglutide / placebo treatment in weight change, abstinence rates and craving assessed by a visual analogue scale (VAS, minimum 1, maximum 10). Additionally, fMRI was performed in a subset of participants and craving and neuronal activity in response to smoking cue videos were examined for gender differences.

Results: Median [IQR] age at inclusion was 42 [32,53] years in females and 44 [34,53] years in males. Mean (SD) BMI was 26.0 (5.0) kg/m² and 28.9 (4.9) kg/m², respectively. After 12 weeks, 61% of females in the dulaglutide and 65% in the placebo group were abstinent, compared to 66% and 64% of male participants. Among quitters, there were no gender differences in absolute or percentual weight change neither on dulaglutide (difference: 0.2 kg, 95%-CI [-1.2, 1.6]; P=0.762 / 0.7%, 95%-CI [-0.9, 2.3]; P= 0.382) nor on placebo treatment (difference: 0.0 kg, 95%-CI [-1.0, 1.0]; P=0.954 / -0.6 %, 95%-CI [-1.8, 0.6]; P=0.340). There is no evidence for either a direct association of gender with change in craving (mean difference females vs. males: 0.05 points, 95%-CI [-1.34, 1.43], P= 0.947) or that the effect of gender on change in craving might depend on dulaglutide treatment (interaction term: P=0.712). Smoking cessation was directly associated with a decline in craving (mean difference quitters vs. persistent smokers: -3.07 points, 95%-CI [-4.67, -1.47], P<0.001); however, this did not depend on gender (interaction term: P=0.380). Data of the fMRI substudy are currently being analyzed and will be presented at the congress.

Conclusion: Our data showed similar abstinence rates, post-cessational weight changes and craving intensity in females and males.