Study of alternative drug to insulin for the treatment of high blood glucose concentration in cardiac surgery patients

Rationale: In the vast majority of patients undergoing cardiac surgery, hyperglycaemia develops during and after surgery. There is a clear association between hyperglycaemia and postoperative complications. The implementation of perioperative insulin treatment is however hampered by risk of hypoglycaemia. Glucagon Like Peptide 1 (GLP-1) therapy is a promising treatment for perioperative hyperglycaemia during cardiac surgery. It has the potential of lowering glucose and reducing the need for insulin therapy, thereby lowering the risk of iatrogenic hypoglycaemia.

Objective: We hypothesize that liraglutide treatment (a GLP-1 analogue), initiated before cardiac surgery, is effective in lowering the number of patients needing perioperative insulin adjustments and reducing the total amount of insulin needed in the perioperative period when aiming for a moderate glucose target of < 8 mmol l-1.

Study design: We will perform a randomized double blind placebo controlled trial in 4 Dutch cardiac surgery centres.

Study population: We will include patients scheduled for elective cardiac surgery, without diabetes mellitus or diabetes mellitus type 2 with a maximal pre-admission total daily insulin treatment dose of ≤0.5 IU kg-1.

Intervention: Patients will be randomized (1:1) to perioperative liraglutide treatment or placebo. Liraglutide or placebo 0.6 mg subcutaneously (sc) the day before surgery and 1.2 mg sc on the day of surgery will be administered. In both arms the glucose target range is <8 mmol l-1.

Main study parameters/endpoints: The main study endpoint is reduction in the number of patients needing perioperative insulin treatment when aiming for plasma glucose < 8 mmol l-1.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: For study purposes, an additional 18.4 ml of blood will be drawn. This will be taken from intravenous or intra-arterial catheters that have been inserted for clinical purposes. Common adverse events with liraglutide treatment are related to the gastrointestinal system, nausea and diarrhoea as reported most frequently. In addition, there is a small risk of hypoglycaemia, which is minimized by frequent glucose monitoring. All adverse events are mostly mild and the drop-out rate from clinical trials due to adverse events has been low. Patient might benefit from this intervention by improved perioperative glucose control without insulin. This reduces hypoglycaemia risk and might reduce other postoperative complications. In general this study will provide more insight in the effect of liraglutide as a glucose-lowering agent to prevent insulin use in the perioperative setting.

We hypothesize that liraglutide treatment, initiated before cardiac surgery, is effective in lowering the number of patients needing perioperative insulin adjustments and reducing the total amount of insulin needed in the perioperative period when aiming for a moderate glucose target of < 8 mmol l-1

Inclusion and informed consent: preoperative clinic.

Randomization: day before surgery

Evening before surgery: liraglutide/placebo 0.6 mg

Day of surgery: liraglutide/placebo 1.2 mg + routine and study laboratory measurements.

Transfer to ICU: stop intervention

30 days after surgery: end follow-up.

Patients will be randomized (1:1) to perioperative liraglutide treatment or placebo. Liraglutide or placebo 0.6 mg subcutaneously (sc) the day before surgery and 1.2 mg sc on the day of surgery will be administered.