Exenatide Infusion During Cardiac Surgery Fails to Improve Outcomes in Large Clinical Trial

A six-year follow-up study challenges the potential of GLP-1 analog therapy to reduce complications during cardiac surgery.

Efforts to improve outcomes in patients undergoing cardiopulmonary bypass-assisted cardiac surgery have led researchers to explore the potential organ-protective effects of exenatide, a glucagon-like peptide-1 (GLP-1) analog commonly used to manage Type 2 diabetes. However, the findings from the recently presented GLORIOUS trial suggest that exenatide, delivered intravenously during surgery, does not significantly reduce risks of death, stroke, or organ failure.

What’s New: Results from the GLORIOUS Trial

The GLORIOUS trial was a randomized, double-blind, placebo-controlled study involving nearly 1,400 patients undergoing coronary bypass grafting or aortic valve replacement at a heart center in Denmark between 2016 and 2021. Patients received either a 6-hour infusion of exenatide or a placebo initiated at the time of anesthesia.

Over a nearly six-year follow-up period, the study found no significant differences in outcomes between the exenatide and placebo groups. Mortality rates were comparable (14% vs. 13%), as were rates of stroke (5.8% vs. 4.8%), new or worsening heart failure (9.8% vs. 10%), and acute kidney injury (4.8% vs. 5.3%).

Dr. Sebastian Wiberg, an anesthesiologist at The Heart Center at Copenhagen University Hospital Rigshospitalet, stated, “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.”

Why It Matters: Addressing an Unmet Need in Cardiac Surgery

Despite advances in surgical techniques and perioperative care, patients undergoing cardiopulmonary bypass remain at risk for complications such as organ injury, inflammation, and blood clot formation. While previous research hinted at the potential protective effects of GLP-1 analogs, the GLORIOUS trial underscores the complexity of improving outcomes in this patient population.

"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," Dr. Wiberg added.

Looking Ahead

The trial provides critical insights into what does and does not work in the high-risk setting of cardiac surgery. However, limitations—such as the study’s single-center design and the use of a single GLP-1 analog—warrant caution when generalizing the results to broader populations or other medications. Dr. Wiberg also emphasized that the effects of longer administration periods, larger doses, or different GLP-1 analogs might be worth exploring in future research.

This study serves as a reminder of the complexities of translating promising preclinical findings into clinical success, particularly in the context of major surgeries involving cardiopulmonary bypass.