Liraglutide for perioperative management of hyperglycaemia in cardiac surgery patients - A multicentre, prospective, randomised superiority trial

Abstract

Introduction Most cardiac surgery patients, with or without diabetes, develop perioperative hyperglycaemia, for which intravenous insulin is the only therapeutic option. This is labour-intensive and carries a risk of hypoglycaemia. We hypothesised that preoperative administration of the glucagon-like peptide-1 receptor agonist liraglutide reduces the number of patients requiring insulin for glycaemic control during cardiac surgery. Methods In this randomised, blinded, placebo-controlled, parallel-group, balanced (1:1), multicentre randomised, superiority 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. Results 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 (129 in the liraglutide group, 132 in the placebo group). In the liraglutide group 55 (43%) patients required additional insulin compared to 80 (61%) patients 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, see figure. We observed no difference in the incidence of hypoglycaemia, nausea and vomiting, mortality, or postoperative complications. Discussion Preoperative liraglutide, compared to placebo, reduces insulin requirements while improving peri-operative glycaemic control during cardiac surgery.