Exenatide infusion fails to mitigate pulmonary decline 3 months post-open-heart surgery

Postoperative pulmonary decline is a common and persistent complication following open-heart surgery, extending beyond the immediate recovery phase. This decline is often driven by inflammation-mediated lung damage and ischemia-reperfusion injury resulting from extracorporeal circulation during procedures like coronary artery bypass grafting (CABG) or surgical aortic valve replacement (SAVR). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promise as protective agents in various inflammatory settings, leading to interest in their potential to mitigate these lung injuries.

This predefined explorative substudy of the GLORIOUS randomized clinical trial included 878 adult patients undergoing non-emergent CABG and/or SAVR. Participants were randomized to receive a continuous infusion of the GLP-1RA, exenatide, or placebo. The infusion was administered during cardiopulmonary bypass and extended into the early postoperative period. Primary endpoints were changes in diffusing capacity of the lung for carbon monoxide (DLCO) and ventilatory performance (FEV1/FVC), measured preoperatively and 3 months postoperatively.

Both diffusing capacity and ventilatory performance exhibited a significant decline 3 months after open-heart surgery. Median DLCO (% predicted corrected) decreased from 80% preoperative to 72% postoperative, representing a -7.7 percentage point (pp) difference (95% CI 6.2 to 9.1; p < 0.001). Similarly, FEV1/FVC declined from 0.75 preoperative to 0.73 postoperative, corresponding to a -1.6 difference (95% CI 1.0 to 2.1; p < 0.001). However, the study found no significant differences in the magnitude of this decline between the exenatide and placebo groups.

All comparisons between exenatide and placebo for DLCO and FEV1/FVC decline showed no statistical significance (all p > 0.3). These findings remained consistent across various subgroup analyses, indicating a lack of protective effect from exenatide in this specific context.