Glucagon in treatment of hypoglycemia – novelties
Authors:
Jan Brož 1; Jana Malinovská 1; Ludmila Brunerová 2; Jana Urbanová 2
Authors‘ workplace:
Interní klinika 2. LF UK a FN Motol, Praha
1; Centrum pro výzkum diabetu, metabolismu a výživy, II. interní klinika 3. LF UK a FNKV, Praha
2
Published in:
Vnitř Lék 2021; 67(2): 103-108
Category:
Overview
Glucagon is actually used in the treatment of severe hypoglycemia. Due to technological difficulties with stability in solution, glucagon in currently available preparations was contained in a form of powder, which needs to be first dissolved in the water before application. This particular administration of glucagon was associated with a certain delay and several mistakes that decreased real amount of glucagon injected in the body. Currently two new formulas of glucagon appeared on the market – first as a stable liquid solution, second as a powder for nasal administration. This article summarizes currently available information about these preparations.
Keywords:
glucagon – hypoglycemia – therapy – diabetes
Sources
1. Schovánek J, Cibíčková L, Čtvrtlík F et al. Diferenciální diagnostika hypoglykemie. Vnitr Lek 2020; 66(2): 129–133.
2. Brož J, Urbanová J.Rámcový pohled na epidemiologii hypoglykemie u diabetes mellitus 1. a 2. typu. Vnitr Lek 2019; 65(4): 55–60.
3. Brož J, Urbanová J, Nunes MA. Současný pohled na léčbu hypoglykemie. Vnitr Lek 2019; 65(4): 61–65.
4. Brož J, Halciaková K, Janíčková Žďárská D et al. Zdravotní způsobilost k řízení motorových vozidel a diabetes mellitus – legislativní změny v r. 2018 a souhrn zdravotních aspektů, Vnitr Lek 2019; 65(4): 82–86.
5. Brunerová L, Urbanová J, Brož J, Hypoglykemie jako symptom adrenální dysfunkce u pacientů s diabetes mellitus – vzácná, ale reálná situace. Vnitr Lek 2019; 65(4): 69–71.
6. Tuháčková M, Urbanová J, Brunerová J et al. Alkohol a riziko hypoglykemie. Vnitr Lek 2019; 65(4): 72–75.
7. [International Hypoglycaemia Study Group]. Glucose Concentrations of Less Than 3.0 mmol/L (54 mg/dL) Should Be Reported in Clinical Trials: A Joint Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2017; 40(1): 155–157. Dostupné z DOI: .
8. Seaquist ER, Anderson J, Childs B et al. Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society. Diabetes Care 2013; 36(5): 1384–1395.
9. Ahrén B. Glucagon-Early breakthroughs and recent discoveries. Peptides. 2015;67:74- 81. doi:10.1016/j.peptides.2015. 03. 011
10. Scott RV, Bloom SR. Problem or solution: The strange story of glucagon. Peptides. 2018;100:36-41. doi:10.1016/j.peptides.2017. 11. 013
11. Rix I, Nexøe‑Larsen C, Bergmann NC, et al. Glucagon Physiology. [Updated 2019 Jul 16]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279127/
12. Langerhansovy ostrůvky 526-530 in Kittnar O a kol. Lékařská fyziologie Praha, Grada Publishing, a. s. 2020, ISBN 978-80-247-9528-7.
13. Christensen M, Vedtofte L, Holst JJ, Vilsboll T, Knop FK. Glucose‑dependent insulinotropic polypeptide: a bifunctional glucose‑dependent regulator of glucagon and insulin secretion in humans. Diabetes 2011; 60: 3103–3109.
14. Hawkes CP, De Leon DD, Rickels MR. Novel Preparations of Glucagon for the Prevention and Treatment of Hypoglycemia. Curr Diab Rep. 2019;19(10):97. Published 2019 Sep 6. doi:10.1007/s11892-019-1216-4
15. Demirbilek H, Hussain K. Congenital Hyperinsulinism: Diagnosis and Treatment Update. J Clin Res Pediatr Endocrinol. 2017; 9(Suppl 2): 69–87. doi:10.4274/jcrpe.2017.S007.
16. Mulla CM, Zavitsanou S, Laguna Sanz AJ, et al. A Randomized, Placebo‑Controlled Double‑Blind Trial of a Closed‑Loop Glucagon System for Postbariatric Hypoglycemia. J Clin Endocrinol Metab. 2020; 105(4): e1260–e1271. doi:10.1210/clinem/dgz197.
17. Peters TM, Haidar A. Dual‑hormone artificial pancreas: benefits and limitations compared with single‑hormone systems. Diabet Med. 2018; 35(4): 450–459. doi:10.1111/ dme.13581.
18. Bi, Y., Atwal, T. & Vege, S.S. Drug Therapy for Acute Pancreatitis. Curr Treat Options Gastro 13, 354–368 (2015). https://doi‑org. ezproxy.is.cuni.cz/10.1007/s11938-015-0058-7.
19. Vindal A, Chander J, Lal P, Mahendra B. Comparison between intraoperative cholangiography and choledochoscopy for ductal clearance in laparoscopic CBD exploration: a prospective randomized study. Surg Endosc. 2015; 29(5): 1030–1038. doi:10.1007/s00464-014-3766-5.
20. Greben SE, Schulman JL. The effect of glucagon on the blood glucose level and the clinical state in the presence of marked insulin hypoglycemia. J Clin Invest. 1957; 36(1 Part 1): 74– 80. doi:10.1172/JCI103412.
21. Ebers DW, Meckel BR. Use of glucagon to terminate insulin reactions in diabetic children. Nebr State Med J. 1958; 43(2): 56–57.
22. Elrick H, Witten TA, Arai Y. (1958). Glucagon Treatment of Insulin Reactions. New England Journal of Medicine, 258(10), 476–480. doi:10.1056/nejm195803062581005.
23. Wiethop BV, Cryer PE. Alanine and Terbutaline in Treatment of Hypoglycemia in IDDM. Diabetes Care 1993; 16(8): 1131–1136.
24. Boido A, Ceriani V, Pontiroli AE. (2014). Glucagon for hypoglycemic episodes in insulin‑treated diabetic patients: a systematic review and meta‑analysis with a comparison of glucagon with dextrose and of different glucagon formulations. Acta Diabetologica, 52(2), 405–412. doi:10.1007/s00592-014-0665-0
25. http://cmp‑manual. wbs.cz/-_leky_-/glucagen-1-mg‑hypokit‑spc. pdf.
26. Hall‑Boyer K, Zaloga GP, Chernow B. Glucagon: hormone or therapeutic agent? Crit Care Med 1974; 12(7): 584–589.
27. 23. Lee H, Hosein EA. Chronic alcohol feeding and its withdrawal on the structure and function of the rat liver plasma membrane: a study with 125I‑ labelled glucagon binding as a metabolic probe. Can J Physiol Pharmacol 1982; 60(9): 1171–1176.
28. American Medical Association. Division of Drugs and Toxicology. Drug evaluations annual 1994. American Medical Association: Chicago 1993. ISBN 0899706029 9780899706023.
29. Eli Lilly and Company. http://cmp‑manual. wbs.cz/-_leky_-/glucagen-1-mg‑hypokit‑spc. pdfGlucagon Emergency Kit. http://www.lillyglucagon.com. Accessed October 29, 2018.
30. Yanai O, Phillip M, Harman I et al. IDDM patients‘ opinions on the use of glucagon emergency kit in severe episodes of hypoglycaemia. Pract Diab Int 1997; 14: 40–42. doi:10.1002/ pdi.1960140204.
31. Mühlhauser I, Berger M, Sonnenberg G, Koch J, Jörgens V, Schernthaner G, Scholz V, Pädagogin D. Incidence and management of severe hypoglycemia in 434 adults with insulin‑dependent diabetes mellitus. Diabetes Care. 1985; 8(3): 268–273. doi: 10.2337/diacare.8. 3. 268.
32. Yale JF, Dulude H, Egeth M et al. Faster use and fewer failures with needle‑free nasal gucagon versus injectable glucagon in severe hypoglycemia rescue: a simulation study. Diabetes Technol Ther 2017; 19(7): 423–432. Dostupné z DOI: http://dx.doi.org/10.1089/dia.2016.0460.
33. Guzman CB, Dulude H, Piché C, Rufiange M, Sadoune AA, Rampakakis E, Carballo D, Triest M, Zhang MX, Zhang S, Tafreshi M, Sicard E. Effects of common cold and concomitant administration of nasal decongestant on the pharmacokinetics and pharmacodynamics of nasal glucagon in otherwise healthy participants: A randomized clinical trial. Diabetes Obes Metab. 2018; 20(3): 646–653.
34. Guzman CB, Dulude H, Piche C et al. Effects of common cold and concomitant administration of nasal decongestant on the pharmacokinetics and pharmacodynamics of nasal glucagon in otherwise healthy participants: A randomized clinical trial. Diabetes Obes Metab.2018; 20: 646–653.
35. Rickels MR, Ruedy KJ, Foster NC et al. Intranasal glucagon for treatment of insulin‑induced hypoglycemia in adults with type 1 diabetes:a randomized crossover noninferiority study. Diabetes Care. 2016; 39: 264–270.
36. Suico J, Hövelmann U, Zhang S et al. Nasal glucagon: a viable alternative to treat insulin‑induced hypoglycaemia in adults with type 1 diabetes. Diabetologia. 2018; 61(Suppl 1): 77–78.
37. Seaquist ER, Dulude H, Zhang XM et al. Prospective study evaluating the use of nasal glucagon for the treatment of moderate to severe hypoglycaemia in adults with type 1 diabetes in a real‑world setting. Diabetes Obes Metab. 2018; 20: 1316–1320.
38. Castle JR, Youssef JE, Branigan D, Newswanger B, Strange P, Cummins M, Shi L, Prestrelski S. Comparative Pharmacokinetic/Pharmacodynamic Study of Liquid Stable Glucagon Versus Lyophilized Glucagon in Type 1 Diabetes Subjects.J Diabetes Sci Technol. 2016 Sep; 10(5): 1101–1107.
39. Xeris Pharmaceuticals. GVOKE US Prescribing Information. 2019. https://www.accessdata. fda.gov/drugsatfda_docs/label/2019/ 212097s000lbl.pdf.
40. Valentine V, Newswanger B, Prestrelski S, Andre AD, Garibaldi M. Human factors usability and validation studies of a glucagon autoinjector in a simulated severe hypoglycemia rescue situation. Diabetes Technol Ther. 2019; 21(9): 522–530.
41. Cummins M, Andre A, Christiansen MP, Newswanger B, Prestrelski S, Junaidi MK. An assessment of usability and drug preparation time for a ready‑to‑use liquid glucagon pen. J Diabetes Sci Technol. 2019; 13: 293–409.
42. Christiansen MP, Cummins M, Prestrelski S, Junaidi MK. A phase 3 comparison of a ready‑to‑use liquid glucagon rescue pen to glucagon emergency kit for the symptomatic relief of severe hypoglycemia. J Diabetes Sci Technol. 2019; 13: 293–409.
43. Beato‑Víbora PI, Arroyo‑Díez FJ. New uses and formulations of glucagon for hypoglycaemia. Drugs Context. 2019; 8: 212599. Published 2019 Jul 30. doi:10.7573/dic.212599.
44. Laffel LM, Limbert C, Phelan H, Virmani A, Wood J, Hofer SE. ISPAD Clinical Practice Consensus Guidelines 2018: Sick day management in children and adolescents with diabetes. Pediatr Diabetes. 2018; 19 Suppl 27(): 193–204.
45. Ranjan A, Schmidt S, Madsbad S, Holst JJ, Nørgaard K. Effects of subcutaneous, low‑dose glucagon on insulin‑ induced mild hypoglycaemia in patients with insulin pump treated type 1 diabetes. Diabetes, Obes Metab. 2016; 18(4): 410–418. doi: 10.1111/dom.12627.
46. Haymond MW, Redondo MJ, McKay S et al. Nonaqueous, Mini‑Dose Glucagon for Treatment of Mild Hypoglycemia in Adults With Type 1 Diabetes: A Dose‑Seeking Study. Diabetes Care. 2016; 39(3): 465–468. doi:10.2337/dc15-2124.
47. Rickels MR, DuBose SN, Toschi E, Beck RW, Verdejo AS, Wolpert H, Cummins MJ, Newswanger B, Riddell MC, T1D Exchange Mini‑Dose Glucagon Exercise Study Group. Mini‑Dose Glucagon as a Novel Approach to Prevent Exercise‑ Induced Hypoglycemia in Type 1 Diabetes. Diabetes Care. 2018; 41(9): 1909–1916.
48. Hövelmann U, Bysted BV, Mouritzen U, Macchi F, Lamers D, Kronshage B, Møller DV, Heise T. Pharmacokinetic and Pharmacodynamic Characteristics of Dasiglucagon, a Novel Soluble and Stable Glucagon Analog.Diabetes Care. 2018; 41(3): 531–537.
49. Pieber TR, Hoevelmann U, Willard J et al. Phase 3 results for dasiglucagon as a fast and effective treatment for severe hypoglycemia. Presented at: American Diabetes Association 79th Scientific Sessions; June 7–11, 2019; San Francisco, CA. Oral Presentation 286-OR.
50. Hövelmann U, Olsen MB, Mouritzen U, Lamers D, Kronshage B, Heise T. Low doses of dasiglucagon consistently increase plasma glucose levels from hypoglycaemia and euglycaemia in people with type 1 diabetes mellitus. Diabetes Obes Metab. 2019; 21(3): 601–610. doi:10.1111/dom.13562.
51. Ranson A, Hövelmann U, Seroussi C, Lamers D, Correia J, Zijlstra E et al. Biochaperone glucagon, a stable ready‑to‑use liquid glucagon formulation enabled by biochaperone technology, is well tolerated and quickly restores euglycemia after insulin‑induced hypoglycemia Advanced Technologies & Treatment for Diabetes; 20–23bruary 2019; Berlin, Germany: 2019.
52. Glezer S, Hovelmann U, Teng S, Lamers D, Odoul M, Correia J et al. BioChaperone glucagon (BCG), a stable ready‑to‑use liquid glucagon formulation, is well tolerated and quickly restores euglycemia after insulin‑induced hypoglycemia. Diabetes. 2018; 67(Supplement 1): 305–OR. 10.2337/db18-305-OR.
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