A recent large-scale clinical trial, known as the GLORIOUS trial, has revealed that intravenous infusion of exenatide, a glucagon-like peptide-1 (GLP-1) analog medication, during heart surgeries involving cardiopulmonary bypass did not significantly reduce the risk of death, stroke, or organ failure. These findings were presented at the American Heart Association's Scientific Sessions 2024.
The GLORIOUS trial aimed to determine if exenatide, a drug primarily used to treat Type 2 diabetes, could mitigate complications during and after cardiac surgery involving cardiopulmonary bypass. This procedure, while essential for maintaining oxygen-rich blood flow to the body's organs during surgery on a non-moving heart, carries risks such as death, stroke, kidney failure, and new or worsening heart failure.
Trial Design and Patient Population
The trial enrolled approximately 1,400 adult patients at a heart center in Denmark between 2016 and 2021. These patients were scheduled for elective or subacute cardiopulmonary bypass-assisted coronary bypass grafting and/or surgical aortic valve replacement. The average age of participants was 68 years, with 17% being female and 98% self-identifying as white. A significant portion of participants had pre-existing heart disease (30%) or heart failure (16%), with nearly 20% having experienced a previous heart attack and 9% a prior stroke.
The study employed a randomized, double-blind, placebo-controlled design. Participants were randomly assigned to receive either a six-hour and 15-minute infusion of 17.4 μg of exenatide or a placebo, initiated at the time of anesthesia prior to surgery. The primary outcome assessed was the incidence of death, stroke, or organ failure.
Key Findings
During the average follow-up period of nearly six years, the study found no statistically significant differences in outcomes between the exenatide and placebo groups:
- 14% of patients receiving exenatide died, compared to 13% in the placebo group.
- Stroke occurred in 5.8% of the exenatide group versus 4.8% of the placebo group.
- New or worsening heart failure was observed in 9.8% of the exenatide group and 10% of the placebo group.
- Acute kidney injury occurred in 4.8% of the exenatide group and 5.3% of the placebo group.
Implications and Future Directions
According to Dr. Sebastian Wiberg, investigator and anesthesiologist at The Heart Centre, Copenhagen University Hospital Rigshospitalet, these findings provide crucial insights into the complexities of cardiac surgery. While the researchers had hoped that exenatide would protect patients from heart failure and other complications, the results indicate that this GLP-1 analog does not offer significant benefits in this setting.
Wiberg also noted that the trial's limitations, including the single-center design and relatively brief administration period of exenatide, may limit the generalizability of the findings. He suggested that future research should explore the potential benefits of different GLP-1 analogs, longer administration periods, or larger doses. The study underscores the ongoing need for clinical trials to identify strategies for optimizing patient health during and after bypass surgery, addressing the significant knowledge gap in perioperative treatment for cardiac surgery patients.
