Peri‐operative management of patients with type‐2 diabetes mellitus undergoing non‐cardiac surgery using liraglutide, glucose–insulin–potassium infusion or intravenous insulin bolus regimens: a randomised controlled trial

Abstract

In this open-label multicentre randomised controlled trial, we investigated three peri-operative treatment strategies to lower glucose and reduce the need for rescue insulin in patients aged 18-75 years with type-2 diabetes mellitus undergoing non-cardiac surgery. Patients were randomly allocated using a web-based randomisation program to premedication with liraglutide (liraglutide group), glucose-insulin-potassium infusion (insulin infusion group) or insulin bolus regimen (insulin bolus group), targeting a glucose < 8.0 mmol.l . The primary outcome was the between group difference in median glucose levels 1 h after surgery. We analysed 150 patients (liraglutide group n = 44, insulin infusion group n = 53, insulin bolus group n = 53) according to the intention-to-treat principle. Median (IQR [range]) plasma glucose 1 h postoperatively was lower in the liraglutide group compared with the insulin infusion and insulin bolus groups (6.6 (5.6-7.7 [4.2-13.5]) mmol.l vs. 7.5 (6.4-8.3 [3.9-16.6]) mmol.l (p = 0.026) and 7.6 (6.4-8.9 [4.7-13.2]) mmol.l ) p = 0.006, respectively). The incidence of hypoglycaemia and postoperative complications did not differ between the groups. Six patients had pre-operative nausea in the liraglutide group, of which two had severe nausea, compared with no patients in the insulin infusion and insulin bolus groups (p = 0.007). The pre-operative administration of liraglutide stabilised peri-operative plasma glucose levels and reduced peri-operative insulin requirements, at the expense of increased pre-operative nausea rates.

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

“…9 A previous trial from our own group in a non-cardiac surgery population showed improved glycaemic control with fewer insulin requirements after preoperative liraglutide administration. 21 Our current data extend these results to patients undergoing cardiac surgery.…”

“…To quantify the effect on insulin requirements, we used an insulin bolus algorithm that was proven effective in controlling perioperative BG concentrations. 21 Besides the intervention group in this study, glycaemic control in the placebo group was also quite good, with a mean intraoperative BG of 7.0 mmol/L and only 4% of patients experiencing hyperglycaemia >11.0 mmol/L. It is probable that the glycaemic control in the placebo group was positively influenced by a clinical trial effect, because outside of clinical trials, non-compliance with insulin protocols results in poorer glycaemic control.…”

“…9 To reduce the risk of preoperative nausea, and based on previous trial experience, we administered the second dose of liraglutide after the induction of anaesthesia. 21 The emetic effects of anaesthesia and surgery probably outweigh any additional impact of liraglutide. 21 Of note, the comparable incidences of postoperative nausea and vomiting in the liraglutide (26%) and placebo groups (20%, P = 0.37) were both considerably lower than the 54% reported in a recent systematic review of postoperative nausea and vomiting after cardiac surgery.…”

“…21 The emetic effects of anaesthesia and surgery probably outweigh any additional impact of liraglutide. 21 Of note, the comparable incidences of postoperative nausea and vomiting in the liraglutide (26%) and placebo groups (20%, P = 0.37) were both considerably lower than the 54% reported in a recent systematic review of postoperative nausea and vomiting after cardiac surgery. 28 Administering prophylactic corticosteroids to treat the systemic inflammatory reaction associated with cardiopulmonary bypass is common practice, 29 as it was in three of the four participating centres in our trial.…”

A Randomized Controlled Trial on the Safety and Efficacy of Exenatide Therapy for the Inpatient Management of General Medicine and Surgery Patients With Type 2 Diabetes

“…In addition, increasing evidence indicates that incretin therapies have cardiovascular benefits, including reduced inflammation and oxidative stress (30,32) and improved endothelial function (24), which could benefit hospitalized patients with diabetes. Previous studies have reported on the use of native GLP-1 and GLP1-RA infusions in critically ill and surgical patients (33)(34)(35). Besch et al (34) compared the use of intravenous exenatide to insulin infusion in cardiac surgery patients and reported similar glycemic control and reduced insulin use in the ICU with exenatide therapy.…”