KEY POINTS:
- Exenatide is a glucaon-like-peptide-1 agonist (GLP-1) improves glycemic control, and other medications in this class, appear to reduce the risk of cardiovascular disease
- The GLORIOUS Trial evaluated intravenous exenatide vs placebo in patients undergoing coronary artery bypass (CABG) or aortic valve replacement (AVR) with cardiopulmonary bypass (CPB)
- After a median follow-up of 5.9 years, no significant difference was observed in composite endpoint death, stroke, renal failure requiring dialysis, and new or worsening heart failure between the exenatide and placebo groups
The GLORIOUS trial presented at the American Heart Association’s annual 2024 conference, investigate whether peri-operative administration of exenatide, a GLP-1 agonist, could reduce the morbidity and mortality in patients undergoing CPB.
GLP-1 agonists reduce the risk of cardiovascular events and kidney disease in patients with type 2 diabetes in large clinical trials, while animal studies suggest they provide myocardial protection from acute myocardial infarction. CPB carries a risk of organ injury and currently, there are no specific pharmacological treatments proven to minimize the risk of organ damage during cardiac surgery.
The randomized, double-blind, placebo-controlled trial was conducted at a single tertiary heart center in Copenhagen Denmark from 2016 to 2021 with follow up through June 2024. Patients undergoing CABG or AVR with CPB were assigned a one-time infusion of exenatide or placebo. The exenatide dosing was standardized and both the treatment and placebo consisted of the same volume (174ml) of sodium chloride solution and added albumen. The infusion kit was prepared to ensure blinding. Nearly 1,400 patients with an average age 68 (17% female, 98% white) were randomized in a 1:1 fashion from 2016 to 2021 with the majority of patients undergoing CABG (68% in the treatment group). Comorbidites between the groups were similar including rates of diabetes (15%)and heart failure (16%).
The primary endpoint was a composite of death, stroke, renal failure requiring dialysis, and new or worsening heart failure, whichever occurred first. Secondary endpoints included among others, time to each individual endpoint. Over a period of almost six years, the primary endpoint occurred in 170 (24%) patients in the exenatide group and 165 (24%) patients in the placebo group, with no significant difference in time to the first primary endpoint (HR 1.0 [95%CI 0.83 – 1.3] nor safety endpoints. Of note, in patients who received exenatide, blood glucose levels were significantly lower with no difference in hypoglycemia between the two groups at 12 hours.
The study concluded that perioperative infusion of exenatide did not improve outcomes in patients undergoing CPB. However, the investigators highlighted the need for further research to determine longer regimens could have a beneficial impact in this population.