Summary: In a large randomised trial in patients undergoing coronary artery bypass grafting or aortic valve replacement, an exenatide infusion during cardiopulmonary bypass did not reduce death, stroke, dialysis-requiring renal failure, or new or worsening heart failure over nearly six years, with no excess adverse events.
PICO Summary
| Element | Detail |
|---|---|
| Population | 1389 predominantly low-risk adults undergoing elective on-pump CABG or aortic valve replacement; single centre, Denmark. |
| Intervention | Infusion of 17.4 µg exenatide during bypass and the first hour after weaning. |
| Comparison | Placebo (2×2 factorial with liberal vs restrictive oxygenation). |
| Outcome | Over a median 5.9 years, a primary composite event (death, stroke, dialysis, or new/worsening heart failure) occurred in 170/24% (exenatide) vs 165/24% (placebo). No significant difference, and no excess adverse events. |
Peri-operative exenatide in cardiac surgery
RCT · on-pump CABG/AVR · 5.9 years
A peri-operative exenatide infusion during cardiopulmonary bypass did not reduce death or major organ failure after CABG or aortic valve replacement over nearly six years, with no safety signal. No role for acute surgical GLP-1 dosing for organ protection.
Expert Commentary
This is a well-conducted, adequately sized negative trial, and I value it for closing off a plausible hypothesis with real data. The rationale was sound, GLP-1 agonists protect the heart and kidney across several cardiovascular settings, so an infusion to blunt the ischaemia-reperfusion insult of cardiopulmonary bypass seemed worth testing. It simply did not work: event rates were essentially identical at 24% in both arms over nearly six years, and reassuringly there was no safety signal either. The honest caveats actually strengthen the message rather than rescue the drug. The population was predominantly low-risk, so event rates were modest and a benefit in sicker patients cannot be entirely excluded, and a single brief peri-operative infusion is a very different exposure from chronic GLP-1 therapy. Can I use this with my patients? Yes, in the sense of not doing something. It tells me there is no basis for using exenatide peri-operatively for organ protection in cardiac surgery, and that the established cardiovascular benefits of this class come from sustained outpatient treatment in appropriate patients, not acute surgical dosing. A clean result that prevents a futile practice.
References
Kjaergaard J, Møller CH, Wiberg S, et al. Efficacy of the glucagon-like peptide-1 agonist exenatide in patients undergoing CABG or aortic valve replacement: a randomized double-blind clinical trial. Circ Cardiovasc Interv. 2025;18(5):e014961. doi:10.1161/CIRCINTERVENTIONS.124.014961