Ultrafast-acting insulins: State of the art

Journal of Diabetes Science and Technology

Volumn 6, Issue 4, 2012, Pages 728-742

  Heinemann, Lutz ^a   Muchmore, Douglas B ^b  

^a Science and Co   (Germany)

^b Halozyme Therapeutics   (United States)

Author keywords

Insulin absorption; Insulin action; Insulin analogs; Insulin pharmacodynamics; Insulin pharmacokinetics; Insulin therapy

Indexed keywords

EXCIPIENT; INSULIN DERIVATIVE; MONOMER; SHORT ACTING INSULIN; ULTRAFAST ACTING INSULIN; UNCLASSIFIED DRUG; ANTIDIABETIC AGENT;

AMINO ACID SEQUENCE; BLOOD FLOW; CONFERENCE PAPER; DIABETIC PATIENT; DISPERSION; DRUG ABSORPTION; DRUG MECHANISM; HUMAN; HYPOGLYCEMIA; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN PUMP; INSULIN TREATMENT; MEAL; METABOLIC REGULATION; NON INSULIN DEPENDENT DIABETES MELLITUS; POSTPRANDIAL STATE; RISK; SUBCUTANEOUS TISSUE; ABSORPTION; CHEMISTRY; DIABETES MELLITUS; DRUG DELIVERY SYSTEM; DRUG DOSAGE FORM; EVALUATION; HEALTH CARE QUALITY; INSTRUMENTATION; INSULIN INFUSION; METHODOLOGY; REVIEW; STANDARD; SUBCUTANEOUS DRUG ADMINISTRATION; TIME;

ABSORPTION; CHEMISTRY, PHARMACEUTICAL; DIABETES MELLITUS; DOSAGE FORMS; DRUG DELIVERY SYSTEMS; HUMANS; HYPOGLYCEMIC AGENTS; INFUSIONS, SUBCUTANEOUS; INSULIN INFUSION SYSTEMS; INSULIN, SHORT-ACTING; STANDARD OF CARE; TIME FACTORS;

EID: 84868019781     PISSN: None     EISSN: 19322968     Source Type: Journal    
DOI: 10.1177/193229681200600402     Document Type: Conference Paper

References (79)

1. Polonsky KS, Given BD, Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J Clin Invest. 1988;81(2):442-8. (Pubitemid 18075238)
2. Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c). Diabetes Care. 2003;26(3):881-5. (Pubitemid 36929359)
3. Monnier L, Colette C, Boniface H. Contribution of postprandial glucose to chronic hyperglycaemia: from the "glucose triad" to the trilogy of "sevens". Diabetes Metab. 2006;32 Spec No2:2S11-6.
4. Siegelaar SE, Holleman F, Hoekstra JB, DeVries JH. Glucose variability; does it matter? Endocr Rev. 2010;31(2):171-82.
5. De Vegt F, Dekker JM, Ruhé HG, Stehouwer CD, Nijpels G, Bouter LM, Heine RJ. Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study. Diabetologia. 1999;42(8):926-31. (Pubitemid 29369599)
6. Temelkova-Kurktschiev TS, Koehler C, Henkel E, Leonhardt W, Fuecker K, Hanefeld M. Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level. Diabetes Care. 2000;23(12):1830-4.
7. McCarter RJ, Hempe JM, Chalew SA. Mean blood glucose and biological variation have greater influence on HbA1c levels than glucose instability: an analysis of data from the Diabetes Control and Complications Trial. Diabetes Care. 2006;29(2):352-5. (Pubitemid 44106517)
8. Kilpatrick ES, Rigby AS, Atkin SL. The effect of glucose variability on the risk of microvascular complications in type 1 diabetes. Diabetes Care. 2006;29(7):1486-90. (Pubitemid 44127568)
9. Kilpatrick ES. Arguments for and against the role of glucose variability in the development of diabetes complications. J Diabetes Sci Technol. 2009;3(4):649-55.
10. Kilpatrick ES, Rigby AS, Atkin SL. Effect of glucose variability on the long-term risk of microvascular complications in type 1 diabetes. Diabetes Care. 2009;32(10):1901-3.
11. Raz I, Wilson PW, Strojek K, Kowalska I, Bozikov V, Gitt AK, Jermendy G, Campaigne BN, Kerr L, Milicevic Z, Jacober SJ. Effects of prandial versus fasting glycemia on cardiovascular outcomes in type 2 diabetes: the HEART2D trial. Diabetes Care. 2009;32(3):381-6.
12. Supersaxo A, Hein WR, Steffen H. Effect of molecular weight on the lymphatic absorption of water-soluble compounds following subcutaneous administration. Pharm Res. 1990;7(2):167-9. (Pubitemid 20208069)
13. Brange J, Owens DR, Kang S, Volund A. Monomeric insulins and their experimental and clinical implications. Diabetes Care. 1990;13(9):923-54. (Pubitemid 20260734)
14. Brange J, Ribel U, Hansen JF, Dodson G, Hansen MT, Havelund S, Melberg SG, Norris F, Norris K, Snel L. Monomeric insulins obtained by protein engineering and their medical implications. Nature. 1988;333(6174):679-82.
15. Heinemann L, Heise T, Wahl LC, Trautmann ME, Ampudia J, Starke AA, Berger M. Prandial glycaemia after a carbohydraterich meal in type I diabetic patients: using the rapid acting insulin analogue [Lys(B28), Pro(B29)] human insulin. Diabet Med. 1996;13(7):625-9. (Pubitemid 26232502)
16. Cobry E, McFann K, Messer L, Gage V, VanderWel B, Horton L, Chase HP. Timing of meal insulin boluses to achieve optimal postprandial glycemic control in patients with type 1 diabetes. Diabetes Technol Ther. 2010;12(3):173-7.
17. Luijf YM, van Bon AC, Hoekstra JB, Devries JH. Premeal injection of rapid-acting insulin reduces postprandial glycemic excursions in type 1 diabetes. Diabetes Care. 2010;33(10):2152-5.
18. Freckmann G, Pleus S, Haug C, Bitton G, Nagar R. Increasing local blood flow by warming the application site: beneficial effects on postprandial glycemic excursions J Diabetes Sci Technol. 2012;6(4):780-5.
19. Dillon RS. Improved serum insulin profiles in diabetic individuals who massaged their insulin injection sites. Diabetes Care. 1983;6(4):399-401. (Pubitemid 13078724)
20. Kellogg DL Jr. In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges. J Appl Physiol. 2006;100(5):1709-18.
21. Minson CT, Berry LT, Joyner MJ. Nitric oxide and neurally mediated regulation of skin blood flow during local heating. J Appl Physiol. 2001;91(4):1619-26. (Pubitemid 32900352)
22. Koivisto VA. Sauna-induced acceleration in insulin absorption. Br Med J. 1980;281(6240):621-2.
23. Sindelka G, Heinemann L, Berger M, Frenck W, Chantelau E. Effect of insulin concentration, subcutaneous fat thickness and skin temperature on subcutaneous insulin absorption in healthy subjects. Diabetologia. 1994;37(4):377-80. (Pubitemid 24113569)
24. Raz I, Weiss R, Yegorchikov Y, Bitton G, Nagar R, Pesach B. Effect of a local heating device on insulin and glucose pharmacokinetic profiles in an open-label, randomized, two-period, one-way crossover study in patients with type 1 diabetes using continuous subcutaneous insulin infusion. Clin Ther. 2009;31(5):980-7.
25. McVey E, Hirsch L, Sutter DE, Kapitza C, Dellweg S, Clair J, Rebrin K, Judge K, Pettis RJ. Pharmacokinetics and postprandial glycemic excursions following insulin lispro delivered by intradermal microneedle or subcutaneous infusion. J Diabetes Sci Technol. 2012;6(4):743-54.
26. Harvey AJ, Kaestner SA, Sutter DE, Harvey NG, Mikszta JA, Pettis RJ. Microneedle-based intradermal delivery enables rapid lymphatic uptake and distribution of protein drugs. Pharm Res. 2011;28(1):107-16.
27. Pettis RJ, Ginsberg B, Hirsch L, Sutter D, Keith S, McVey E, Harvey NG, Hompesch M, Nosek L, Kapitza C, Heinemann L. Intradermal microneedle delivery of insulin lispro achieves faster insulin absorption and insulin action than subcutaneous injection. Diabetes Technol Ther. 2011;13(4):435-42.
28. Pettis RJ, Hirsch L, Kapitza C, Nosek L, Hovelmann U, Kurth HJ, Sutter DE, Harvey NG, Heinemann L. Microneedle-based intradermal versus subcutaneous administration of regular human insulin or insulin lispro: pharmacokinetics and postprandial glycemic excursions in patients with type 1 diabetes. Diabetes Technol Ther. 2011;13(4):443-50.
29. Gupta J, Felner EI, Prausnitz MR. Rapid pharmacokinetics of intradermal insulin administered using microneedles in type 1 diabetes subjects. Diabetes Technol Ther. 2011;13(4):451-6.
30. Boss AH, Petrucci R, Lorber D. Coverage of prandial insulin requirements by means of an ultra-rapid-acting inhaled insulin. J Diabetes Sci Technol. 2012;6(4):773-9.
31. Heinemann L, Heise T. Current status of the development of inhaled insulin. Br J Diab Vasc Dis. 2004;4:295-301. (Pubitemid 39462106)
32. Richardson PC, Boss AH. Technosphere insulin technology. Diabetes Technol Ther. 2007;9 Suppl 1:S65-72.
33. Rave K, Potocka E, Heinemann L, Heise T, Boss AH, Marino M, Costello D, Chen R. Pharmacokinetics and linear exposure of AFRESA compared with the subcutaneous injection of regular human insulin. Diabetes Obes Metab. 2009;11(7):715-20.
34. Rave K, Heise T, Pfutzner A, Boss AH. Coverage of postprandial blood glucose excursions with inhaled technosphere insulin in comparison to subcutaneously injected regular human insulin in subjects with type 2 diabetes. Diabetes Care. 2007;30(9):2307-8. (Pubitemid 47359038)
35. Rosenstock J, Lorber DL, Gnudi L, Howard CP, Bilheimer DW, Chang PC, Petrucci RE, Boss AH, Richardson PC. Prandial inhaled insulin plus basal insulin glargine versus twice daily biaspart insulin for type 2 diabetes: a multicentre randomised trial. Lancet. 2010;375(9733):2244-53.
36. Heinemann L, Jacques Y. Oral insulin and buccal insulin: a critical reappraisal. J Diabetes Sci Technol. 2009;3(3):568-84.
37. Stote R, Marbury T, Shi L, Miller M, Strange P. Comparison pharmacokinetics of two concentrations (0.7% and 1.0%) of Nasulin, an ultra-rapid-acting intranasal insulin formulation. J Diabetes Sci Technol. 2010;4(3):603-9.
38. Stote R, Miller M, Marbury T, Shi L, Strange P. Enhanced absorption of Nasulin™, an ultrarapid-acting intranasal insulin formulation, using single nostril administration in normal subjects. J Diabetes Sci Technol. 2011;5(1):113-9.
39. Hingson RA, Hughes JG. Clinical studies with jet injection; a new method of drug administration. Curr Res Anesth Analg. 1947;26(6):221-30.
40. Weller C, Linder M. Jet injection of insulin vs the syringe-andneedle method. JAMA. 1966;195(10):844-7.
41. Taylor R, Home PD, Alberti KG. Plasma free insulin profiles after administration of insulin by jet and conventional syringe injection. Diabetes Care. 1981;4(3):377-9. (Pubitemid 12201587)
42. Bremseth DL, Pass F. Delivery of insulin by jet injection: recent observations. Diabetes Technol Ther. 2001;3(2):225-32. (Pubitemid 32651958)
43. Malone JI, Lowitt S, Grove NP, Shah SC. Comparison of insulin levels after injection by jet stream and disposable insulin syringe. Diabetes Care. 1986;9(6):637-40. (Pubitemid 17208945)
44. Theintz GE, Sizonenko PC. Risks of jet injection of insulin in children. Eur J Pediatr. 1991;150(8):554-6.
45. Sarno MJ, Bell J, Edelman SV. Pharmacokinetics and glucodynamics of rapid-, short-, and intermediate-acting insulins: comparison of jet injection to needle syringe. Diabetes Technol Ther. 2002;4(6):863-6. (Pubitemid 36169241)
46. Engwerda EE, Abbink EJ, Tack CJ, de Galan BE. Improved pharmacokinetic and pharmacodynamic profile of rapid-acting insulin using needle-free jet injection technology. Diabetes Care. 2011;34(8):1804-8.
47. Edsberg B, Herly D, Hildebrandt P, Kühl C. Insulin bolus given by sprinkler needle: effect on absorption and glycaemic response to a meal. Br Med J (Clin Res Ed). 1987;294(6584):1373-6. (Pubitemid 17078937)
48. Pohl R, Hauser R, Li M, DeSouza E, Feldstein R, Seibert R, Ozhan K, Kashyap N, Steiner S. Ultra-rapid absorption of recombinant human insulin induced by zinc chelation and surface charge masking. J Diabetes Sci Technol. 2012;6(4):755-63.
49. Krasner A, Pohl R, Simms P, Pichotta P, Hauser R, De Souza E. A review of a family of ultra-rapid-acting insulins: formulation development. J Diabetes Sci Technol. 2012;6(4):786-96.
50. Steiner S, Hompesch M, Pohl R, Simms P, Flacke F, Mohr T, Pfutzner A, Heinemann L. A novel insulin formulation with a more rapid onset of action. Diabetologia. 2008;51(9):1602-6.
51. Hompesch M, McManus L, Pohl R, Simms P, Pfutzner A, Bulow E, Flacke F, Heinemann L, Steiner SS. Intra-individual variability of the metabolic effect of a novel rapid-acting insulin (VIAject) in comparison to regular human insulin. J Diabetes Sci Technol. 2008;2(4):568-71.
52. Heinemann L, Hompesch M, Flacke F, Simms P, Pohl R, Albus K, Pfützner A, Steiner S. Reduction of postprandial glycemic excursions in patients with type 1 diabetes: a novel human insulin formulation versus a rapid-acting insulin analog and regular human insulin. J Diabetes Sci Technol. 2011;5(3):681-6.
53. Heinemann L, Nosek L, Flacke F, Albus K, Krasner A, Pichotta P, Heise T, Steiner S. U-100, pH-Neutral formulation of VIAject(®): faster onset of action than insulin lispro in patients with type 1 diabetes. Diabetes Obes Metab. 2012;14(3):222-7.
54. Muchmore DB, Vaughn DE. Accelerating and improving the consistency of rapid-acting analog insulin absorption and action for both subcutaneous injection and continuous subcutaneous infusion using recombinant human hyaluronidase. J Diabetes Sci Technol. 2012;6(4):764-72.
55. Bookbinder LH, Hofer A, Haller MF, Zepeda ML, Keller GA, Lim JE, Edgington TS, Shepard HM, Patton JS, Frost GI. A recombinant human enzyme for enhanced interstitial transport of therapeutics. J Control Release. 2006;114(2):230-41. (Pubitemid 44291844)
56. Vaughn DE, Yocum RC, Muchmore DB, Sugarman BJ, Vick AM, Bilinsky IP, Frost GI. Accelerated pharmacokinetics and glucodynamics of prandial insulins injected with recombinant human hyaluronidase. Diabetes Technol Ther. 2009;11(6):345-52.
57. Hompesch M, Muchmore DB, Morrow L, Vaughn DE. Accelerated insulin pharmacokinetics and improved postprandial glycemic control in patients with type 1 diabetes after coadministration of prandial insulins with hyaluronidase. Diabetes Care. 2011;34(3):666-8.
58. Hompesch M, Muchmore DB, Morrow L, Ludington E, Vaughn DE. Improved postprandial glycemic control in patients with type 2 diabetes from subcutaneous injection of insulin lispro with hyaluronidase. Diabetes Technol Ther. 2012;14(3):218-24.
59. Vaughn DE, Muchmore DB. Use of recombinant human hyaluronidase to accelerate rapid insulin analogue absorption: experience with subcutaneous injection and continuous infusion. Endocr Pract. 2011;17(6):914-21.
60. Morrow L, Muchmore DB, Ludington EA, Vaughn DE, Hompesch M. Reduction in intrasubject variability in the pharmacokinetic response to insulin after subcutaneous co-administration with recombinant human hyaluronidase in healthy volunteers. Diabetes Technol Ther. 2011;13(10):1039-45.
61. Phillips NB, Whittaker J, Ismail-Beigi F, Weiss MA. Insulin fibrillation and protein design: Topological resistance of single-chain analogs to thermal degradation with application to a pump reservoir. J Diabetes Sci Technol. 2012;6(2):277-88.
62. Heinemann L, Overmann H, Mühlhauser I. How do patients with diabetes mellitus type I handle the injection-meal interval in daily life? Diabetes. 1997;46 Suppl 1:340A.
63. Overmann H, Heinemann L. Injection-meal interval: recommendations of diabetologists and how patients handle it. Diabetes Res Clin Pract. 1999;43(2):137-42. (Pubitemid 29155658)
64. Heinemann L, Hohmann A, Starke AAR, Berger M. What is the correct timing of subcutaneous injections of regular insulin to cover carbohydrate rich meals? Horm Metab Res Suppl. 1992;26:137-9. (Pubitemid 23017887)
65. Coates PA, Ismail IS, Luzio SD, Griffiths I, Ollerton RL, Volund A, Owens DR. Intranasal insulin: the effects of three dose regimens on postprandial glycaemic profiles in type II diabetic subjects. Diabet Med. 1995;12(3):235-9.
66. Rave K, Bott S, Heinemann L, Sha S, Becker RH, Willavize SA, Heise T. Time-action profile of inhaled insulin in comparison with subcutaneously injected insulin lispro and regular human insulin. Diabetes Care. 2005;28(5):1077-82. (Pubitemid 40616616)
67. Heinemann L, Weyer C, Rauhaus M, Heinrichs S, Heise T. Variability of the metabolic effect of soluble insulin and the rapidacting insulin analog insulin aspart. Diabetes Care. 1998;21(11):1910-4. (Pubitemid 28478292)
68. Becker RH, Frick AD. Clinical pharmacokinetics and pharmacodynamics of insulin glulisine. Clin Pharmacokinet. 2008;47(1):7-20. (Pubitemid 350260885)
69. Rave KM, Nosek L, de la Peña A, Seger M, Ernest CS 2nd, Heinemann L, Batycky RP, Muchmore DB. Dose response of inhaled dry-powder insulin and dose equivalence to subcutaneous insulin lispro. Diabetes Care. 2005;28(10):2400-5. (Pubitemid 41384284)
70. Heise T, Nosek L, Spitzer H, Heinemann L, Niemoller E, Frick AD, Becker RH. Insulin glulisine: a faster onset of action compared with insulin lispro. Diabetes Obes Metab. 2007;9(5):746-53. (Pubitemid 47261856)
71. Mudaliar SR, Lindberg FA, Joyce M, Beerdsen P, Strange P, Lin A, Henry RR. Insulin aspart (B28 asp-insulin): a fast-acting analog of human insulin: absorption kinetics and action profile compared with regular human insulin in healthy nondiabetic subjects. Diabetes Care. 1999;22(9):1501-6. (Pubitemid 29418246)
72. Rave K, Heise T, Heinemann L, Boss AH. Inhaled Technosphere insulin in comparison to subcutaneous regular human insulin: time action profile and variability in subjects with type 2 diabetes. J Diabetes Sci Technol. 2008;2(2):205-12.
73. Luzio SD, Dunseath G, Lockett A, Broke-Smith TP, New RR, Owens DR. The glucose lowering effect of an oral insulin (Capsulin) during an isoglycaemic clamp study in persons with type 2 diabetes. Diabetes Obes Metab. 2010;12(1):82-7.
74. Cernea S, Kidron M, Wohlgelernter J, Modi P, Raz I. Comparison of pharmacokinetic and pharmacodynamic properties of single-dose oral insulin spray and subcutaneous insulin injection in healthy subjects using the euglycemic clamp technique. Clin Ther. 2004;26(12):2084-91. (Pubitemid 40353618)
75. Cernea S, Kidron M, Wohlgelernter J, Modi P, Raz I. Dose-response relationship of oral insulin spray in healthy subjects. Diabetes Care. 2005;28(6):1353-7. (Pubitemid 40756696)
76. Heinemann L, Hompesch M. Biosimilar insulins: how similar is similar? J Diabetes Sci Technol. 2011;5(3):741-54.
77. Muchmore D, Sharp M, Vaughn D. Benefits of blinded continuous glucose monitoring during a randomized clinical trial. J Diabetes Sci Technol. 2011;5(3):676-80.
78. Bergenstal RM, Tamborlane WV, Ahmann A, Buse JB, Dailey G, Davis SN, Joyce C, Perkins BA, Welsh JB, Willi SM, Wood MA. Sensor-augmented pump therapy for A1C reduction (STAR 3) study: results from the 6-month continuation phase. Diabetes Care. 2011;34(11):2403-5.
79. Heinemann L. Continuous glucose monitoring and clinical trials. J Diabetes Sci Technol. 2009;3(4):981-5.