Intravenous infusion of exenatide, a GLP-1 analog medication, during heart surgeries involving bypass did not significantly reduce the risk of death, stroke or organ failure, according to results from one arm of the GLORIOUS trial presented at AHA 2024. Results from a second arm of the study exploring oxygenation strategies for organ protection in heart surgery were also presented as late-breaking science.

The GLORIOUS trial randomized approximately 1,400 adults who had cardiopulmonary bypass-assisted coronary bypass grafting and/or SAVR at a single heart center in Denmark between 2016 and 2021 to receiving either a six hour and 15-minute infusion of exenatide or a placebo prior to surgery.

Overall results found no significant differences in outcomes between the two groups over an average follow-up period of nearly six years. Broken down by event, 14% of patients who received exenatide died during the follow-up period compared with 13% of those who received the placebo. Stroke occurred in 5.8% of patients in the exenatide group vs. 4.8% of those in the placebo group, while new or worsening heart failure after surgery occurred in 9.8% vs. 10%, respectively. Acute kidney injury occurred in 4.8% of those receiving exenatide during initial hospital admission compared with 5.3% of patients receiving placebo.

"We had hoped exenatide might protect patients from developing heart failure or other common complications after heart bypass surgery, however, the results suggest that this GLP-1 analog does not offer significant benefits," said Sebastian Wiberg, MD, PhD, when presenting the findings."There is still a big gap in knowledge about how to best support patients on bypass during surgery, and there is an urgent need for more clinical trials to find ways to optimize patient health during and after bypass surgery."

Wiberg noted that because the trial assessed the effects of a single treatment with exenatide over a relatively brief administration period at one heart center in Denmark, the results may not be generalizable to other medications among different patient populations. Additionally, he said, it's possible that different GLP-1 analogs, longer periods of administration, or larger doses may potentially be beneficial for patients undergoing cardiopulmonary bypass-assisted cardiac surgery.

In the separate arm of the study, a restrictive oxygenation strategy during cardiopulmonary bypass-assisted coronary bypass grafting and/or SAVR and weaning of cardiopulmonary bypass in adult patients did not reduce mortality or morbidity from renal failure, stroke or heart failure."We followed the participants for a median of 5.9 years until a total of 323 events had occurred as planned ... and we found no significant difference between the two treatment groups," said Wiberg.