Increasing evidence suggests that tight glycemic control improves clinical outcomes after coronary artery bypass grafting (CABG). However, the risk for hypoglycemia with insulin often results in less aggressive glycemic control. Glucagon-like peptide-1 (GLP-1) is a naturally occurring peptide whose insulinotropic effects are predicated on the glucose concentration, minimizing the risk for hypoglycemia. This study was conducted to examine whether perioperative treatment with GLP-1 would affect glycemic control and improve hemodynamic recovery after CABG. Twenty patients with coronary heart disease and preserved left ventricular function who were scheduled to undergo CABG were randomized to receive standard therapy at the discretion of the surgeon or treatment with GLP-1 (1.5 pmol/kg/min) as a continuous infusion beginning 12 hours before CABG and continuing for 48 hours. Perioperative hemodynamics, the left ventricular ejection fraction, plasma glucose, and requirements for insulin drips and inotropic support were monitored. There were no differences between groups in the preoperative, postoperative, or 7-day left ventricular ejection fraction (GLP-1 61 +/- 4%, control 59 +/- 3%) or cardiac index at 18 hours (GLP-1 3.0 +/- 0.2 L/min/m(2), control 3.3 +/- 0.4 L/min/m(2)). However, the control group required greater use of inotropic and vasoactive infusions during the 48 hours after the operation to achieve the same hemodynamic result. There were also more frequent arrhythmias requiring antiarrhythmic agents in the control group. GLP-1 resulted in better glycemic control in the pre- and perioperative periods (GLP-1 95 +/- 3 mg/dl, control 140 +/- 10 mg/dl, p </=0.02), with 45% less insulin requirements to achieve the same glycemic control in the postoperative period (GLP-1 139 +/- 4 mg/dl, control 140 +/- 3 mg/dl). In conclusion, the perioperative use of GLP-1 achieves better glycemic control and comparable hemodynamic recovery without the requirements for high-dose insulin or inotropes.