Glucagon-like Peptide 1 Agonist Exenatide for Improved Glucose Control and Cardiac Function in Patients With Aortocoronary Bypass (Executive)

Glucagon-like Peptide 1 Agonist Exenatide for Improved Glucose Control and Cardiac Function in Patients With Aortocoronary Bypass

EXEnatide in Patients Undergoing Coronary Artery Bypass Grafting for Improved glUcose conTrol and hemodynamIc ValuEs

GLP-1 has not only beneficial effects on glucose metabolism but also direct positive effects on cardiac function and metabolism in both experimental models and in patients with type 2 diabetes mellitus. Clinical data on the effects of GLP-1 agonists on cardiac function and glucose control in patients undergoing cardiac surgery are not known. Based on the results of experimental studies there is a potential for exenatide to positively influence both cardiac function and glucose metabolism in cardiac surgery patients with and without type 2 diabetes mellitus. The primary endpoint of this study is to examine whether pre- and peri-operative administration of exenatide affects perioperative hemodynamics, echocardiographic parameters, necessity of antiarrhythmic and inotropic treatment and glucose control in patients with coronary atherosclerosis and decreased left ventricular function undergoing elective coronary artery bypass grafting operation (CABG). In addition, safety and tolerability of peri-operative administration of exenatide in these patients will be examined as a secondary study objective.

Patients with decreased left ventricular function undergoing elective coronary artery by-pass grafting receiving perioperatively i.v. exenatide on top of standard treatment

Patients with decreased left ventricular function undergoing elective coronary artery by-pass grafting receiving standard treatment

Perioperative continuous i.v. administration of exenatide lasting for 72 hours - 40 ng/min for initial 30 min, 20 ng/min for remaining 71.5 hours

cardiac chamber dimensions left ventricular systolic function left ventricular diastolic function right ventricular systolic function

Inclusion Criteria: elective coronary artery bypass grafting operation (CABG) decreased left ventricular (LV) systolic function (EF LV ≤ 50%) Age 18 to 85 Signed informed consent Females with childbearing potential have to use appropriate contraceptive measures during the whole study period and 6 months after terminating exenatide infusion (hormonal contraception or double-barrier contraception for both partners) Exclusion Criteria: allergy to exenatide allergy to insulin mental incapacity or language barrier use of incretin-based therapies <3 months before inclusion in the study diabetic ketoacidosis established autonomic neuropathy history of acute pancreatitis or severe disease of digestive tract renal failure (preoperative creatinine ≥ 180 umol/l) liver failure (coagulation times more than 1.5 times higher without use of anticoagulants) cardiac surgical procedure on valve, thoracic aorta or MAZE procedure pregnancy and lactation

Lips M, Mraz M, Klouckova J, Kopecky P, Dobias M, Krizova J, Lindner J, Diamant M, Haluzik M. Effect of continuous exenatide infusion on cardiac function and peri-operative glucose control in patients undergoing cardiac surgery: A single-blind, randomized controlled trial. Diabetes Obes Metab. 2017 Dec;19(12):1818-1822. doi: 10.1111/dom.13029. Epub 2017 Jul 31.