Liraglutide May Reduce Postprandial Hyperglycemia in Closed Loop Setting

BOSTON — Adding once daily liraglutide to insulin in a closed loop system may have the potential to reduce postprandial hyperglycemia as well as insulin requirements, as compared with closed loop insulin monotherapy, according to a new study presented the American Diabetes Association (ADA) 75th Scientific Sessions. 

“We are aware of the limitations of a closed loop system,” study researcher Jeniece Trast, RN, of the Children’s Hospital at Montefiore in Bronx, New York, said during a presentation. “These limitations are due to the fact that the current algorithm used in the closed loop system cannot respond in a timely enough manner to glucose absorption resulting from a meal.”

She noted that liraglutide is a long-acting, 24-hour, glucagon-like peptide-1 (GLP-1) receptor agonist with a half life of 13 hours that can reduce postprandial hyperglycemia.

“The mechanism of action is a glucose-dependent insulin secretion delay in gastric emptying and a decrease in glucagon secretion,” she said.

Trast and colleagues therefore hypothesized that suppressing meal-related hyperglucagonemia with a GLP-1 agonist such as once daily subcutaneous liraglutide in the closed loop setting could be a novel way of combating postprandial hyperglycemia without hypoglycemia.

The researchers conducted a small study with a randomized, open-label, crossover design in 15 patients with type 1 diabetes in which they compared adjuvant liraglutide plus insulin with insulin monotherapy using an external physiologic insulin delivery (ePID) closed loop system.

Patients were aged 18 to 40 years and had type 1 diabetes for more than 1 year and be on insulin therapy.

The researchers randomly assigned patients to two overnight visits. Study A involved treatment with insulin and Study B involved treatment with insulin plus liraglutide 1.2 mg administered before dinner on day 1.

Results indicated that the glycemic profile was significantly better in the insulin plus liraglutide arm, as compared with the insulin only arm (P<.05). Insulin plus liraglutide was also associated with overall delayed time to peak blood glucose levels without significant postprandial hypoglycemia, as compared with insulin only in patients with type 1 diabetes (P<.0001).

“In summary, this study found that closed loop with once daily liraglutide decreased postprandial hyperglycemia and postprandial glucagonemia and delayed time to and magnitude of peak blood glucose levels with no significant hypoglycemia after meals,” Trast said. “When using liraglutide, insulin values were significantly lower after meals and we saw a decrease in peak after meal times. We also saw a significant decrease in glucagon levels after meal times.”

This was a proof of concept study, Trast noted, and future trials are needed to confirm these findings.

Reference

1. Trast J et al. Abstract 220-OR: Liraglutide Reduces Postprandial Hyperglycemia in the Closed Loop System. Presented at: American Diabetes Association (ADA) 75th Scientific Sessions; June 5-9, 2015; Boston.