Liraglutide for perioperative management of hyperglycaemia in cardiac surgery patients: a multicentre randomized superiority trial

Abstract

Aims 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 hypothesized 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. Materials and methods In this randomized, blinded, placebo‐controlled, parallel‐group, balanced (1:1), multicentre randomized, superiority trial, adult patients undergoing cardiac surgery in four Dutch tertiary hospitals were randomized 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 >8.0 mmol/L in the operating theatre. Research pharmacists used centralized, stratified, variable‐block, randomization software. Patients, care providers and study personnel were blinded to treatment allocation. Results Between June 2017 and August 2018, 278 patients were randomized 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 with 80 (61%) in the placebo group and absolute difference 18% (95% confidence interval 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. Conclusions Preoperative liraglutide, compared with placebo, reduces insulin requirements while improving perioperative glycaemic control during cardiac surgery.

Management of diabetes and hyperglycaemia in the hospital

“…[94][95][96] Findings from randomised controlled trials suggest preoperative treatment with liraglutide can improve glycaemic control in the perioperative period in patients with and without diabetes (table 2). 88,91,97 In a study of non-ICU patients with type 2 diabetes, treatment with exenatide plus basal insulin resulted in a higher proportion of glucose readings within the target range of 3•9-10•0 mmol/L (78%) compared with exenatide alone (62%) or basalbolus insulin (63%). 68 As expected, trials with GLP-1 receptor agonists have shown increased frequencies of gastrointestinal side-effects.…”

“…68 As expected, trials with GLP-1 receptor agonists have shown increased frequencies of gastrointestinal side-effects. 68,88,91,97 More research is needed with these drugs to determine if the potential for improved glycaemic control with a reduction of hypoglycaemic events counterbalances the increase in gastrointestinal side-effects in the hospital setting.…”

“…45,47 Results from other trials also suggest the potential benefits of GLP-1 receptor agonists on glycaemic control during the immediate perioperative period (table 2). 88,91 Studies with DPP-4 inhibitors have not been able to meaningfully reduce the incidence of hyperglycaemia in the perioperative period and are not recommended for this purpose. The US Food and Drug Administration (FDA) recently recommended to withhold SGLT2 inhibitors 3-4 days before surgery because of the potential risk of euglycaemic diabetic ketoacidosis.…”

Sitagliptin for the prevention and treatment of perioperative hyperglycaemia in patients with type 2 diabetes undergoing cardiac surgery: A randomized controlled trial

“…The primary outcome was insulin administration for BG greater than 8.0 mmol/L (144 mg/dL) in the operating theatre. A lower proportion of patients in the liraglutide group required additional insulin compared with placebo (43% vs. 61%, absolute difference: 18%, P = .003) 30 . Liraglutide, a DPP‐4–resistant GLP‐1 analogue, is a more potent agent than sitagliptin and may explain the differences between ours and the former study (30).…”

Preoperative Management of Endocrine, Hormonal, and Urologic Medications: Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement

“…In the perioperative setting, small studies have evaluated the use of GLP-1 during cardiac and noncardiac surgery and have shown effectiveness in achieving glycemic control while decreasing insulin requirements. [28][29][30] Counter to these benefits, increased nausea when using liraglutide the night before surgery has been reported. 29 We identified no studies in which the safety of these agents was assessed in patients undergoing surgery involving bowel manipulation where peristalsis and gastric emptying might be affected.…”