GLP-1 infusions improve glycemic control, cardiac function in surgical patients

June 7, 2009

The utility of continuous GLP-1 infusion in major surgery is demonstrated by rapid and dramatic lowering of glucose followed by maintenance of euglycemia in patients with type 2 diabetes undergoing major abdominal surgery who receive an 8-hour infusion of GLP-1 compared to saline infusion.

Infusion of glucagon-like peptide (GLP)-1 has favorable clinical and metabolic effects in the surgical setting, says Dana K. Andersen, MD.

The utility of continuous GLP-1 infusion in major surgery is demonstrated by rapid and dramatic lowering of glucose followed by maintenance of euglycemia in patients with type 2 diabetes undergoing major abdominal surgery who receive an 8-hour infusion of GLP-1 compared to saline infusion.

"This is very interesting to us in surgery because we happen to be firm believers in the concept of tight glycemic control," says Dr. Andersen, professor of surgery, Johns Hopkins University, Baltimore. Compared with conventional insulin therapy, intensive glycemic control has been shown to significantly reduce the incidence of death in surgical patients, especially those undergoing cardiac surgery.

"The mortality of these patients was literally halved by the intensive insulin therapy, and most of this benefit was due to the dramatic reduction in sepsis," he says. "This seemed to coincide with the period of maintaining euglycemia, which prevents the overgrowth of pathogenic bacteria or which improves organ function, or both, so as to reduce the risk of infection or death."

Cardiac surgeons have understood the value of tight glycemic control for years, in the form of dramatic improvement in outcomes, says Dr. Andersen. This observation suggests that incretins-GLP-1 or GLP-1 mimetics-may have a therapeutic role in cardiac patients, which is supported by data showing that GLP-1 improved left ventricular function and wall motion scores in patients presenting with acute myocardial infarction who underwent primary percutaneous coronary intervention. Preliminary evidence also indicates that GLP-1 may provide benefits in the treatment of heart failure.

In patients undergoing coronary artery bypass graft surgery, the use of GLP-1 starting before the surgery and extended to 3 days after surgery resulted in better glycemic control and a dramatic reduction in the need for inotropic agents. In animal models of dilated cardiomyopathy, the metabolite of GLP-1 (GLP 9-36) improved cardiac output, left ventricular ejection fraction, and arterial pressures. "The metabolite was virtually just as effective as the intact molecule given by intravenous infusion in these test animals," he says. "That raises the possibility that the metabolite of GLP-1 may in fact be a metabolically active compound."

This effectiveness of GLP 9-36 is maintained in GLP-1-receptor knockout mice, which suggests that GLP 9-36 may interact with a novel class of receptors separate from the GLP-1 receptor. Further evidence suggests that GLP 9-36 may also be metabolically active in glucose metabolism.

Examination of the effects of synthetic GLP 9-36 in lean and obese individuals has found suppression of hepatic glucose production, particularly in the obese individuals.