The glucoregulatory benefits of glucagon-like peptide-1 (7-36) amide infusion during intensive insulin therapy in critically ill surgical patients: a pilot study

Abstract

Objectives: Intensive insulin therapy for tight glycemic control in critically ill surgical patients has been shown to reduce mortality; however, intensive insulin therapy is associated with iatrogenic hypoglycemia and increased variability of blood glucose levels. The incretin glucagon-like peptide-1 (7-36) amide is both insulinotropic and insulinomimetic and has been suggested as an adjunct to improve glycemic control in critically ill patients. We hypothesized that the addition of continuous infusion of glucagon-like peptide-1 to intensive insulin therapy would result in better glucose control, reduced requirement of exogenous insulin administration, and fewer hypoglycemic events.

Design: Prospective, randomized, double-blind, placebo-controlled clinical trial.

Setting: Surgical or burn ICU.

Patients: Eighteen patients who required intensive insulin therapy.

Interventions: A 72-hour continuous infusion of either glucagon-like peptide-1 (1.5 pmol/kg/min) or normal saline plus intensive insulin therapy.

Measurements and main results: The glucagon-like peptide-1 cohort (n = 9) and saline cohort (n = 9) were similar in age, Acute Physiology and Chronic Health Evaluation score, and history of diabetes. Blood glucose levels in the glucagon-like peptide-1 group were better controlled with much less variability. The coefficient of variation of blood glucose ranged from 7.2% to 30.4% in the glucagon-like peptide-1 group and from 19.8% to 56.8% in saline group. The mean blood glucose coefficient of variation for the glucagon-like peptide-1 and saline groups was 18.0% ± 2.7% and 30.3% ± 4.0% (p = 0.010), respectively. The 72-hour average insulin infusion rates were 3.37 ± 0.61 and 4.57 ± 1.18 U/hr (p = not significant). The incidents of hypoglycemia (≤ 2.78 mmol/L) in both groups were low (one in the glucagon-like peptide-1 group, three in the saline group).

Conclusions: Glucagon-like peptide-1 (7-36) amide is a safe and efficacious form of adjunct therapy in patients with hyperglycemia in the surgical ICU setting. Improved stability of blood glucose is a favorable outcome, which enhances the safety of intensive insulin therapy. Larger studies of this potentially valuable therapy for glycemic control in the ICU are justified.

Conflict of interest statement

The remaining authors have disclosed that they do not have any potential conflicts of interest.

Figures

Figure 1

Glucose profile and insulin infusion rate during insulin infusion therapy in a patient receiving saline (left) and a patient receiving glucagon-like peptide-1 (right).

Figure 2

Average glucose profiles (hourly, upper) and insulin infusion rates (4-hour averages, bottom) during insulin infusion therapy for nine patients receiving saline (dotted lines) and for the nine patients receiving glucagon-like peptide (GLP)-1 (solid lines).

Figure 3

Plasma C-peptide levels (upper) and glucagon levels (lower) in patients receiving insulin infusion therapy who also received a 72-hour infusion of glucagon-like peptide (GLP)-1 (solid lines) or saline (dotted lines).