56-OR: Liraglutide for Perioperative Management of Hyperglycaemia in Cardiac Surgery Patients (GLOBE): A Multicentre, Prospective, Superiority Randomised Trial

Abstract

Background: Most cardiac surgery patients develop perioperative hyperglycaemia requiring intravenous insulin therapy. This is labour-intensive and carries a risk of hypoglycaemia. We hypothesised that preoperative administration of the GLP-1 receptor agonist liraglutide would reduce the number of patients requiring insulin during cardiac surgery. Methods: In this randomised, blinded, placebo-controlled, parallel-group, balanced (1:1), superiority, multicentre randomised trial, adult patients undergoing cardiac surgery in four Dutch tertiary hospitals 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. Blood glucose was measured hourly and controlled using an insulin-bolus-algorithm. The primary outcome was insulin administration for blood glucose above 8·0 mmol/L in the operating theatre. Research pharmacists used centralised, stratified, variable-block, randomisation software. Patients, care providers, and study personnel were blinded to treatment allocation. Findings: Between June 2017 and August 2018, 278 patients were randomised to liraglutide (139) or placebo (139). All patients receiving at least one study drug injection were included in the intention-to-treat analyses (liraglutide: 129, placebo: 132). In the liraglutide group, 55 patients (43%) required additional insulin compared to 80 patients (61%) in the placebo group, absolute difference: 18% (95% CI 5·9-30·0, p=0·003). Dose and number of insulin injections and mean blood glucose were all significantly lower in the liraglutide group. We observed no difference in the incidence of hypoglycaemia, nausea and vomiting, mortality, or postoperative complications. Interpretation: Preoperative liraglutide reduces insulin requirements while improving peri-operative glycaemic control during cardiac surgery. Disclosure A.H. Hulst: Research Support; Self; Novo Nordisk A/S. B. Preckel: Research Support; Self; Novo Nordisk Inc. M.W. Hollmann: Consultant; Self; Eurocept BV. Other Relationship; Self; CSL Behring. J. DeVries: Advisory Panel; Self; Novo Nordisk A/S. Employee; Self; Profil Institute for Metabolic Research. Speaker's Bureau; Self; Novo Nordisk A/S. J. Hermanides: Consultant; Self; Julius Clinical (CRO). Research Support; Self; Novo Nordisk A/S. Funding Novo Nordisk A/S