Research Highlights:

• The GLORIOUS trial found that an intravenous infusion of exenatide, a glucagon-like peptide-1 (GLP-1) during heart surgeries involving bypass did not result in significant benefits at preventing death, stroke or organ injury compared to a placebo.
• Researchers noted, however, additional research is needed to determine if there are any benefits from other GLP-1 medications or from administration of exenatide for a longer period of time or at a larger dose than was tested in this study.
• Note: The study featured in this news release is a research abstract. Abstracts presented at American Heart Association’s scientific meetings are not peer-reviewed, and the findings are considered preliminary until published as full manuscripts in a peer-reviewed scientific journal.

Embargoed until 8:17 a.m. CT/9:17 a.m. ET, Sunday, Nov. 17, 2024

This news release contains updated information from the researcher that was not in the abstract.

(NewMediaWire) - November 17, 2024 - CHICAGO — 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.

Study details, background and design:

• The GLORIOUS trial included 1,389 adult patients scheduled for elective or subacute cardiopulmonary bypass-assisted coronary bypass grafting and/or surgical aortic valve replacement between February 2016 and December 2021 at a heart center in Denmark.
• Participants had 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 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, including death, kidney failure requiring renal replacement therapy, stroke, new-onset heart failure, hospital readmission for heart failure or other cardiovascular causes, surgical site infection, hypoglycemia, pancreatitis, a relative reduction of ejection fraction by 50% compared to baseline, reoperation for bleeding or other causes, and post-surgery myocardial infarction.

Co-authors, disclosures and funding sources are listed in the abstract.

Statements and conclusions of studies that are presented at the American Heart Association’s scientific meetings are solely those of the study authors and do not necessarily reflect the Association’s policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. Abstracts presented at the Association’s scientific meetings are not peer-reviewed, rather, they are curated by independent review panels and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting. The findings are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal.

 The Association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific Association programs and events. The Association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers and health insurance providers and the Association’s overall financial information are available here.

Additional Resources:

• Multimedia is available on the right column of the release link.
• Link to abstract; and AHA Scientific Sessions 2024 Online Program Planner
• AHA news release: Major CVD event risk cut by 20% in adults without diabetes, with overweight or obesity (November 2023)
• For more news at AHA Scientific Sessions 2024, follow us on X @HeartNews, #AHA24

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