Mixed results for sitagliptin, liraglutide for perioperative management of hyperglycemia during cardiac surgery

SAN FRANCISCO — Two studies presented at the American Diabetes Association Scientific Sessions yield mixed results for the use of approved diabetes therapies for perioperative management of hyperglycemia in patients undergoing cardiac surgery.

Perioperative hyperglycemia is reported in more than 80% of patients with type 2 diabetes after cardiac surgery. Although the recommended treatment for perioperative hyperglycemia is continuous insulin infusion, it can be labor intensive and is associated with hypoglycemia risk, according to Saumeth Cardona, MD, MPH, associate director of research projects, division of endocrinology, metabolism and lipids at Emory University School of Medicine.

“Previous randomized controlled studies have shown that administration of a DPP-IV inhibitor alone or in combination with basal insulin is effective in improving glycemic control in patients with type 2 diabetes [undergoing] general surgery,” Cardona told Endocrine Today.

Cardona and colleagues conducted a randomized, double-blind trial to examine the effect of sitagliptin (Januvia, Merck) for preventing and treating hyperglycemia after coronary artery bypass graft (CABG) surgery. In total, 202 patients were randomly assigned once-daily sitagliptin (n = 101) or placebo (n = 101), starting the day before surgery and continued in the ICU after transition to regular wards. Three-quarters of patients were men, mean age was 64 years, mean BMI was 32 kg/m² and mean diabetes duration was 10 years. More than half of the CABG procedures were elective.

The frequency of hyperglycemia (> 180 mg/dL) was not significantly different with sitagliptin or placebo, at about 65% during surgery (P = .47 for comparison), 80% in the ICU (P = .14) and 85% after transition to the telemetry unit (P = .39), Cardona said during the presentation.

Glycemic control was similar in the sitagliptin and placebo groups before or during surgery, ICU stay or after transition to telemetry, according to results presented here.

The researchers reported no differences in the proportion of patients requiring insulin therapy in the ICU (placebo, 67% vs. sitagliptin, 69%; P = .75) or after transition to the telemetry unit (placebo, 91% vs. sitagliptin, 85%; P = .35). Patients assigned sitagliptin had lower subcutaneous insulin requirements after the transition from IV insulin, with no increased risk for hyperglycemia or hypoglycemia, compared with placebo.

“The study showed that patients receiving sitagliptin had lower need of insulin — total daily dose and units per kilogram per day — compared to placebo after transition to regular flow,” Cardona told Endocrine Today.

The frequency of hypoglycemia was low, with less than 10% of patients having at least one episode of hypoglycemia in the ICU, Cardona said. There were no severe episodes of hypoglycemia after the transition from IV to subcutaneous insulin.

In other results, in-hospital complications, including acute kidney injury, cardiovascular complications, readmission, length of stay and mortality, were similar between the sitagliptin and placebo groups.

“Our study indicates that the administration of sitagliptin during the perioperative period in patients undergoing CABG surgery failed to improve glycemic control, prevent the need for insulin administration or rate of hospital complications during the hospital stay compared to placebo,” Cardona told Endocrine Today. “Unfortunately, sitagliptin treatment prior to and during the hospital stay has little impact in improving glycemic control in patients with diabetes undergoing cardiac surgery.”

In another study presented at the ADA Scientific Sessions, Abraham H. Hulst, MD, from the department of anesthesiology at Amsterdam UMC, and colleagues evaluated perioperative administration of the GLP-1 receptor agonist liraglutide (Victoza, Novo Nordisk).

The randomized, blinded, placebo-controlled, parallel-group GLOBE study enrolled adults undergoing elective cardiac surgery at four tertiary hospitals in the Netherlands. The perioperative strategy was as follows: 0.6 mg subcutaneous liraglutide the night before cardiac surgery and 1.2 mg after induction of anesthesia compared with matching placebo.

In total, 278 patients were randomly assigned perioperative liraglutide (n = 139) or placebo (n = 139). Patients were primarily men, mean age was 64 years and mean BMI was 27 kg/m².

Need for additional insulin, to target glucose less than 144 mg/dL, was required by 43% in the liraglutide group vs. 61% in the placebo group (P = .003), Hulst said during his presentation.

Moreover, dose, number of insulin injections and mean blood glucose were significantly lower in the liraglutide group, compared with placebo, according to the new data.

The researchers observed no difference in hypoglycemia, mortality and postoperative complications between the two perioperative strategies. Hulst noted that nausea and vomiting were “fairly low,” at about 25%, “which is, in a postoperative surgery cohort, a lot lower than normal.”

Hulst said use of perioperative liraglutide appears to be a “worthwhile intervention” in this population and noted that investigation will continue. – by Katie Kalvaitis and Jill Rollet

Reference s :

Cardona S, et al. 60-OR.

Hulst AH, et al. 56-OR. Both presented at: American Diabetes Association 79th Scientific Sessions; June 7-11, 2019; San Francisco.

Disclosures: Cardona reports no relevant financial disclosures. Hulst reports he receives research support from Novo Nordisk.