Liraglutide as an alternative to insulin for glycemic control in intensive care unit: A randomized, open-label, clinical study
Yashpal Singh, Monish Nakra, Vishesh Verma, K. Shankar, Amit Nachankar, K.V.S. Kumar
hyperglycemia, insulin, Intensive Care Unit, liraglutide,Critical care
Citation Information :
Singh Y, Nakra M, Verma V, Shankar K, Nachankar A, Kumar K. Liraglutide as an alternative to insulin for glycemic control in intensive care unit: A randomized, open-label, clinical study. Indian J Crit Care Med 2017; 21 (9):568-572.
Background: Intravenous insulin is the cornerstone in the management of hyperglycemia in the Intensive Care Unit (ICU). We studied the efficacy of liraglutide compared with insulin in the ICU.
Materials and Methods: In this prospective, open-labeled, randomized study, we included 120 patients (15–65 years, either sex) admitted to ICU with capillary blood glucose (CBG) between 181 and 300 mg/dl. We excluded patients with secondary diabetes and APACHE score >24. The patients were divided into two groups (n = 60) based on the CBG: Group 1 (181–240) and Group 2 (241–300). They were randomized further into four subgroups (n = 30) to receive insulin (Groups 1A and 2A), liraglutide (Group 1B), and insulin with liraglutide (Group 2B). The primary outcome was the ability to achieve CBG below 180 mg/dL at the end of 24 h. The secondary outcomes include mortality at 1 month and hospital stay. Data and results were analyzed using Mann-Whitney U-test, paired t- test, and Chi-square tests.
Results: The mean age of the patients (93M and 27F) was 57.1 ± 13.9 years, hospital stay (16.9 ± 7.5 days), and CBG was 240.5 ± 36.2 mg/dl. The primary outcome was reached in 26, 27, 25, and 28 patients of Groups 1A, 2A, 1B, and 2B, respectively. The 30-day mortality and hospital stay were similar across all the four groups. Hypoglycemia was common with insulin and gastrointestinal side effects were more common with liraglutide (P < 0.001).
Conclusion: Liraglutide is a viable alternative to insulin for glycemic control in the ICU. Further studies with a larger number of patients are required to confirm our findings.
Falciglia M, Freyberg RW, Almenoff PL, D'Alessio DA, Render ML. Hyperglycemia-related mortality in critically ill patients varies with admission diagnosis. Crit Care Med 2009;37:3001-9.
Marik PE, Bellomo R. Stress hyperglycemia: An essential survival response! Crit Care Med 2013;41:e93-4.
van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001;345:1359-67.
Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, et al. Intensive insulin therapy in the medical ICU. N Engl J Med 2006;354:449-61.
Nice-Sugar Study Investigators, Finfer S, Chittock DR, Su SY, Blair D, Foster D, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009;360:1283-97.
Preiser JC, Devos P, Ruiz-Santana S, Mélot C, Annane D, Groeneveld J, et al. A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult Intensive Care Units: The glucontrol study. Intensive Care Med 2009;35:1738-48.
Kovalaske MA, Gandhi GY. Glycemic control in the medical Intensive Care Unit. J Diabetes Sci Technol 2009;3:1330-41.
Turchin A, Matheny ME, Shubina M, Scanlon JV, Greenwood B, Pendergrass ML, et al. Hypoglycemia and clinical outcomes in patients with diabetes hospitalized in the general ward. Diabetes Care 2009;32:1153-7.
Umpierrez GE, Schwartz S. Use of incretin-based therapy in hospitalized patients with hyperglycemia. Endocr Pract 2014;20:933-44.
Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375:311-22.
Schwartz S, DeFronzo RA. Is incretin-based therapy ready for the care of hospitalized patients with type 2 diabetes? The time has come for GLP-1 receptor agonists! Diabetes Care 2013;36:2107-11.
Meier JJ, Weyhe D, Michaely M, Senkal M, Zumtobel V, Nauck MA, et al. Intravenous glucagon-like peptide 1 normalizes blood glucose after major surgery in patients with type 2 diabetes. Crit Care Med 2004;32:848-51.
American Diabetes Association. Standards of medical care in diabetes–2014. Diabetes Care 2014;37 Suppl 1:S14-80.
Qaseem A, Humphrey LL, Chou R, Snow V, Shekelle P, Clinical Guidelines Committee of the American College of Physicians, et al. Use of intensive insulin therapy for the management of glycemic control in hospitalized patients: A clinical practice guideline from the American college of physicians. Ann Intern Med 2011;154:260-7.
Marso SP, Al-Amoodi M, Riggs L, House JA, Hamburg MS, Kennedy KF, et al. Administration of intravenous Exenatide to patients with sustained hyperglycemia in the coronary ICU (Abstract). Diabetes 2011;60:A75.
Parks M, Rosebraugh C. Weighing risks and benefits of liraglutide – The FDA's review of a new antidiabetic therapy. N Engl J Med 2010;362:774-7.
Polderman JA, Houweling PL, Hollmann MW, DeVries JH, Preckel B, Hermanides J, et al. Study protocol of a randomised controlled trial comparing perioperative intravenous insulin, GIK or GLP-1 treatment in diabetes-PILGRIM trial. BMC Anesthesiol 2014;14:91.
DeFronzo RA, Sherwin RS, Felig P. Synergistic interactions of counterregulatory hormones: A mechanism for stress hyperglycemia. Acta Chir Scand Suppl 1980;498:33-42.
Cathy L, Julie S, Katie W. Stress and diabetes: A review of the links. Diabetes Spectr 2005;18:121-7.
Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM, Kitabchi AE, et al. Hyperglycemia: An independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab 2002;87:978-82.
Singh AK, Singh R. SAVOR-TIMI to SUSTAIN-6: A critical comparison of cardiovascular outcome trials of antidiabetic drugs. Expert Rev Clin Pharmacol 2017;10:429-42.
Abuannadi M, Kosiborod M, Riggs L, House JA, Hamburg MS, Kennedy KF, et al. Management of hyperglycemia with the administration of intravenous exenatide to patients in the cardiac Intensive Care Unit. Endocr Pract 2013;19:81-90.
King AB, Philis-Tsimikas A, Kilpatrick ES, Langbakke IH, Begtrup K, Vilsbøll T, et al. A fixed ratio combination of insulin degludec and liraglutide (IDegLira) reduces glycemic fluctuation and brings more patients with type 2 diabetes within blood glucose target ranges. Diabetes Technol Ther 2017;19:255-64.