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.
1Department of Medicine, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, Baltimore, MD.
2Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, Baltimore, MD.
3Clinical Physiology Branch, National Institute on Aging, Baltimore, MD.
4Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.
Drs. Galiatsatos and Gibson contributed equally to this work. Drs. Galiatsatos, Gibson, Rabiee, Carlson, Egan, and Elahi assisted in the conduct of the study. Drs. Gibson, Shannon, Andersen, and Elahi designed the study. Dr. Elahi wrote the first draft of the article. All other authors contributed to the writing of the article.
Dr. Gibson received support for research from The Society of Critical Care Medicine and Jahnigan Award of the American Geriatrics Society. Dr. Shannon consulted for Merck, Pfizer, and AstraZeneca/Bristol-Myers Squibb and is a board member with ABIM. He lectured for IRSW, BOMC Institute for Heart care Improvement (visiting professor). He has a patent with Ventrigen, LCC (founder). His institution received grant support from Pfizer and AstraZeneca/Bristol-Myers Squibb. Dr. Andersen is employed by Johns Hopkins University and the National Institutes of Health and consulted for Z-Medica (member scientific advisory board). He is a board member with the Association for Academic Surgery Foundation and lectured at scientific meetings and medical centers. He receives royalties from McGraw Hill (member, editorial board, textbook). Dr. Elahi consulted for Merck. The remaining authors have disclosed that they do not have any potential conflicts of interest.
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