A large-scale clinical trial, known as GLORIOUS, has found that intravenous infusion of exenatide, a glucagon-like peptide-1 (GLP-1) analog, during heart surgeries involving cardiopulmonary bypass did not significantly reduce the risk of death, stroke, or organ failure. The findings were presented at the American Heart Association’s Scientific Sessions 2024.
Exenatide is a medication primarily used to treat Type 2 diabetes, receiving FDA approval in 2005. The GLORIOUS trial aimed to determine if exenatide could mitigate complications during and after cardiac surgery involving cardiopulmonary bypass, a procedure where blood is circulated through a machine to oxygenate it while the heart is temporarily stopped for surgery.
Trial Design and Results
The GLORIOUS trial was a randomized, double-blind, placebo-controlled study conducted at a heart center in Denmark between 2016 and 2021. It included approximately 1,400 adult patients undergoing cardiopulmonary bypass-assisted coronary bypass grafting and/or surgical aortic valve replacement. Participants were randomly assigned 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.
Expert Commentary
According to investigator Sebastian Wiberg, M.D., Ph.D., an anesthesiologist at The Heart Centre, Copenhagen University Hospital Rigshospitalet in Copenhagen, Denmark, "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."
Wiberg also noted, "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."
Study Limitations and Future Directions
Wiberg emphasized that the trial assessed the effects of a single treatment with exenatide over a relatively brief administration period at one heart center in Denmark. Therefore, the results may not be generalizable to other medications among different patient populations. He added that 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.
Patient Demographics and Baseline Characteristics
The GLORIOUS trial included 1,389 adult patients with an average age of 68 years, 17% were female, and 98% self-identified as white. At the beginning of the study, 30% of participants had heart disease, and 16% had heart failure. Nearly 20% of participants had had a previous heart attack, and 9% had a previous stroke.
Participants were randomized to receive an infusion of either 17.4μg of exenatide or placebo infusion initiated at the time of anesthesia prior to surgery. The infusion for both groups of patients lasted six hours and 15 minutes. Participants were monitored during surgery and approximately 6 years (5.9-years) of follow-up health information was collected for various outcomes after surgery.
