No significant benefit of IV exenatide in reducing complications during cardiac surgery, finds GLORIOUS trial

A large-scale clinical trial found that intravenous infusion of exenatide, a glucagon-like peptide-1 (GLP-1) analog medication, during heart surgeries involving bypass did not significantly reduce the risk of death, stroke or organ failure. Researchers presented this preliminary late-breaking science trial today at the American Heart Association’s Scientific Sessions 2024. The meeting, Nov. 16-18, 2024, in Chicago, is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science.

Exenatide is a GLP-1-like (analog) medication primarily prescribed to treat Type 2 diabetes, approved by the U.S. Food and Drug Administration in 2005. The GLORIOUS trial tested whether intravenous infusion of exenatide could reduce complications during and after cardiac surgery that included the assistance of cardiopulmonary bypass.

Health care professionals frequently perform heart surgery with the assistance of cardiopulmonary bypass, also known as a heart-lung machine. During this procedure, the blood is drained from the veins through a pump, passed through an oxygenator that adds oxygen and removes carbon dioxide, and pumped back into the body through the aorta. The process allows the body and organs to continue to receive oxygen-rich blood and function, while the surgeon operates on a non-moving heart. While helpful, there are still risks to bypass, including death, stroke, kidney failure and new or worsening heart failure. Previous research has suggested that exenatide might have organ-protective effects, the authors noted.

“The evidence for perioperative treatment of patients undergoing cardiac surgery is limited,” said investigator Sebastian Wiberg, M.D., Ph.D., an anesthesiologist at The Heart Centre, Copenhagen University Hospital Rigshospitalet in Copenhagen, Denmark. “As such, there is a large unmet need for clinical trials investigating strategies to optimize treatment and reduce the risk of complications, such as organ injury, inflammation and the formation of blood clots.”

The GLORIOUS trial included approximately 1,400 adults who had cardiopulmonary bypass-assisted coronary bypass grafting and/or surgical aortic valve replacement at a heart center in Denmark between 2016 and 2021, with the final follow-up visit completed in June of 2024. The study was a randomized, double-blind, placebo-controlled clinical trial, meaning participants were randomly assigned to receive a test treatment or a sham/placebo treatment, and neither the researchers nor the participants knew which group participants were in. Patients were randomized to one of two groups: to receive either a six hour and 15-minute infusion of exenatide or a placebo prior to surgery.

The study found no significant differences in outcomes between the two groups during the average follow-up period of nearly six years:

• 14% of patients who received exenatide died during the follow-up period vs. 13% of those who received the placebo.
• 5.8% of patients in the exenatide group had a stroke vs. 4.8% of those in the placebo group.
• 9.8% of patients who received exenatide had new or worsening heart failure after surgery vs. 10% of those who received the placebo.
• 4.8% in the exenatide group had acute kidney injury during the initial hospital admission for surgery vs. 5.3% in the placebo group.

“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. Of note, these findings provide important insights into what does and doesn’t work in the complex setting of cardiac surgery,” Wiberg said. “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 emphasized 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. In addition, it’s possible that different GLP-1 analogs, administration for a longer period of time or a larger dose may potentially be beneficial for patients undergoing cardiopulmonary bypass-assisted cardiac surgery.