Blood pressure changes during smoking cessation in a randomized, double-blind, placebo-controlled trial of dulaglutide treatment

Aims Cigarette smoking cessation reduces cardiovascular risk via various mechanisms. Thereby, the role of blood pressure remains unclear, with studies reporting both decreased and increase blood pressure values after cessation, potentially influenced by weight change. We previously showed that the glucagon like peptide-1 analogue dulaglutide mitigates weight gain after smoking cessation. This secondary analysis investigates the effect of smoking cessation on blood pressure changes in dulaglutide- vs. placebo-treated individuals. We hypothesized a beneficial effect of smoking cessation on blood pressure, particularly in dulaglutide-treated participants.Methods and results This is a predefined secondary analysis of a randomized, double-blind, placebo-controlled trial. Participants (n = 255) underwent a 12-week smoking cessation programme including standard of care (behavioural counselling and varenicline) with weekly injections of dulaglutide 1.5 mg or placebo, followed by a follow-up of 52 weeks. The primary outcome was change in systolic blood pressure after 52 weeks in abstinent vs. smoking individuals. Further outcomes included blood pressure and body weight changes at Week 12 and 52 according to smoking status and treatment arms. A path analysis was performed to estimate direct and indirect effect of different variables on systolic blood pressure changes. Two hundred and eighteen out of 255 participants with complete blood pressure readings were included in the analyses. Across the entire study population, systolic blood pressure was stable over the period of 52 weeks after smoking cessation despite a weight gain of +3 kg (0, 5.4) at Week 52. Blood pressure reductions were seen in the subgroups of participants with minimal weight gain <= 3 kg [-4.6 mmHg (-9, 3)] and in individuals with hypertensive blood pressure values at baseline [-16 mmHg (-22, 2)]. Dulaglutide treatment reduced body weight and blood pressure initially, followed by a weight rebound and a blood pressure increase of +7.5 mmHg (-1, 15) at Week 52. The path analysis identified weight as an important factor influencing blood pressure during smoking cessation.Conclusion Our analysis suggests that smoking cessation may have a beneficial effect on blood pressure- especially in hypertensive individuals-, counteracting the expected blood pressure increase caused by post-cessation weight gain. However, it also underlines the importance of weight control after smoking cessation as a crucial factor in smoking cessation.Registration ClinicalTrials.gov: NCT 03204396. This study investigated how smoking cessation and a 12-week use of the weight-loss drug dulaglutide compared with placebo affected blood pressure and weight over a 52-week period. Smoking cessation was associated with an average weight gain of 4.2 kg after 52 weeks.Despite this weight gain, blood pressure remained stable over the study period and even decreased in the subgroup of hypertensive participants.Dulaglutide initially reduced weight and blood pressure at Week 12, but these benefits were followed by weight rebound and increases in blood pressure after the drug was stopped.