Effects of Liraglutide on Myocardial Function After Cardiac Surgery: A Secondary Analysis of the Randomised Controlled GLOBE Trial

Abstract

Introduction: Previous studies demonstrated the cardioprotective properties of glucagon-like peptide-1 receptor agonists in patients with diabetes or cardiac disease. We investigated whether preoperative subcutaneous liraglutide improves myocardial function after cardiac surgery. Methods: We performed a pre-planned secondary analysis of adult patients undergoing cardiac surgery included in the GLOBE trial. Patients were randomised to receive 0.6 mg subcutaneous liraglutide on the evening before surgery and 1.2 mg after induction of anaesthesia, or matching placebo. Perioperative echocardiographic assessments, haemodynamic parameters, doses of vasoactive inotropic support and postoperative measurements of troponin, Creatine Kinase-MB , creatinine and lactate were compared between groups. Results: The study population consisted of the entire intention-to-treat cohort of the GLOBE trial. In this study, 129 patients received liraglutide and 132 patients placebo. Baseline characteristics were comparable between groups. Postoperatively, 170 (65%) patients underwent echocardiography. In the liraglutide group, more patients had a normal left ventricular systolic function (68%, 59 patients) compared to placebo (53%, 44 patients), difference = 15%, 95%CI = 0-30, p = 0.049. Assessment of the right ventricle revealed no difference in function. Conclusions: Patients receiving short-term preoperative liraglutide treatment better maintained normal myocardial function after cardiac surgery. This study warrants further evaluation of the potential beneficial effects of GLP-1 receptor agonists in cardiac surgery patients.

Effects of Liraglutide on Left Ventricular Function: A Meta-Analysis of Randomized, Placebo-Controlled Trials

“…After a title and abstract screening, another 60 citations were excluded as reviews, meeting abstracts, commentaries, case reports, or irrelevant studies. Among the 20 full-text review articles, ten were further excluded for reasons such as substudy [14], registering as one trial [15], comparing with other drugs, or no available data for pooling [16,17]. Finally, ten placebocontrolled RCTs [18][19][20][21][22][23][24][25][26][27] involving a total of 732 cases were included in the meta-analysis.…”

Glucagon‐like peptide‐1 receptor agonists: a narrative review of clinical pharmacology and implications for peri‐operative practice

“…Glucagon-like peptide-1 receptors are localised primarily to the sinoatrial node [47,48]. Glucagon-like peptide-1 receptors found in arterial walls are important in the function of the endothelium and the autonomic nervous system [19].…”

Preoperative considerations of new long-acting glucagon-like peptide-1 receptor agonists in diabetes mellitus

“…increased HR found in all studies administering GLP-1 RAs, it is unlikely to be the explanation for any of the cardioprotective properties. 15,17 Thus far, cardioprotective mechanisms are poorly understood. Animal studies showed increases in myocardial metabolic efficiency of glucose usage, lower vascular resistances in pulmonary and systemic circulations, and activation of ischaemic preconditioning pathways.…”

“…Animal studies showed increases in myocardial metabolic efficiency of glucose usage, lower vascular resistances in pulmonary and systemic circulations, and activation of ischaemic preconditioning pathways. 16,17 In humans, the relevance of these findings remains unclear, despite some promising results of improved left ventricular function and reduced infarct size after ischaemic injury in GLP-1 RA-treated subjects. 18,19 What remains, however, are the findings from major cardiovascular outcome trials (Table 1) that found clear cardiovascular benefits with reduced rates of myocardial infarction, stroke, and revascularisation procedures.…”