Zusammenfassung
Das erste inhalative Insulin wurde durch die zuständigen US-amerikanischen und europäischen Behörden im Januar 2006 zugelassen, womit dem Thema der alternativen Insulinapplikation in der diabetologischen Praxis zunehmend Bedeutung zukommt. Der vorliegende Beitrag erläutert die unterschiedlichen methodisch-technologischen Strategien, die bei der Entwicklung von inhalativem Insulin verfolgt werden, und gibt einen Überblick über die verfügbare klinische Literatur. Daneben wird auf künftige Entwicklungen im Bereich der oralen Insuline eingegangen.
Abstract
The first inhalational insulin was approved by American and European authorities in January 2006. Thus, the topic of alternative insulin application is of rising importance for diabetic patients and diabetes specialists. This review provides information on the different technological strategies of inhalational insulin development and gives an overview of the available clinical publications. In addition, the current knowledge on oral insulin formulations is presented.
Literatur
Arbit E, Nosek L, Kapitza C et al. (2004) Oral insulin as first-line therapy in type 2 diabetes: a randomized-controlled pilot study. Diabetologia [Suppl 1] 47: A5
Cefalu WT, Skyler JS, Kourides IA et al. (2001) Inhaled human insulin treatment in patients with type 2 diabetes mellitus. Ann Intern Med 134: 203–207
Clement S, Still GJ, Kosutic G (2002) The effects of timing of a standardized meal on absorption of a single oral dose of hexyl-insulin monoconjugate (HIM2) in patients with type 1 diabetes. Diabetes [Suppl 2] 51: A49
Cook MN, Girman CJ, Stein PP et al. (2005) Glycemic control continues to deteriorate after sulfonylureas are added to metformin among patients with type 2 diabetes. Diabetes Care 28: 995–1000
DeFronzo RA, Bergenstal RM, Cefalu WT et al. (2005) Efficacy of inhaled insulin in patients with type 2 diabetes not controlled with diet and exercise: a 12-week, randomized, comparative trial. Diabetes Care 28: 1922–1928
Fineberg SE, Kawabata T, Finco-Kent D et al. (2005) Antibody response to inhaled insulin in patients with type 1 or type 2 diabetes. J Clin Endocrinol Metab 90: 3287–3294
Freemantle N, Blonde L, Duhot D et al. (2005) Availability of inhaled insulin promotes greater perceived acceptance of insulin therapy in patients with type 2 diabetes. Diabetes Care 28: 427–428
Gale EA (2001) Two cheers for inhaled insulin. Lancet 357: 324–325
Gelfand RA, Schwartz SL, Horton ML et al. (1998) Pharmacological reproducibility of inhaled human insulin pre-meal dosing in patients with type 2 diabetes mellitus. Diabetes [Suppl 1] 47: A99
Heinemann L, Heise T (2004) Current status of the development of inhaled insulin. Br J Diabetes Vasc Dis 4: 295–301
Heinemann L, Traut T, Heise T (1997) Time-action profile of inhaled insulin. Diabet Med 14: 63–72
Heinemann L, Klappoth W, Rave K et al. (2000) Intra-individual variability of the metabolic effect of inhaled insulin together with an absorption enhancer. Diabetes Care 23: 1343–1347
Heise T, Heinemann L (2001) Rapid and long-acting insulin analogues as an approach to improve insulin therapy: an evidence-based medicine assessment. Curr Pharmaceut Design 7: 1303–1325
Heise T, Bott S, Tusek C et al. (2005) The effect of insulin antibodies on the metabolic action of inhaled and subcutaneous insulin: a prospective randomized pharmacodynamic study. Diabetes Care 28: 2161–2169
Henry RR, Mudaliar SR, Howland WC et al. (2003) Inhaled insulin using the AERx insulin diabetes management system in healthy and asthmatic subjects. Diabetes Care 26: 764–769
Hermansen K, Ronnemaa T, Petersen AH et al. (2004) Intensive therapy with inhaled insulin via the AERx insulin diabetes management system: a 12-week proof-of-concept trial in patients with type 2 diabetes. Diabetes Care 27: 162–167
Himmelmann A, Jendle J, Mellen A et al. (2003) The impact of smoking on inhaled insulin. Diabetes Care 26: 677–682
Hollander PA, Blonde L, Rowe R et al. (2004) Efficacy and safety of inhaled insulin (Exubera) compared with subcutaneous insulin therapy in patients with type 2 diabetes: results of a 6-month, randomized, comparative trial. Diabetes Care 27: 2356–2362
Hunt LM, Valenzuela MA, Pugh JA (1997) NIDDM patients‘ fears and hopes about insulin therapy: the basis of patient reluctance. Diabetes Care 20: 292–298
Jendle JH, Karlberg BE (1996) Effects of intrapulmonary insulin in patients with non-insulin-dependent diabetes. Scan J Clin Lab Invest 56: 555–561
Kapitza C, Arbit E, Abbas R et al. (2003) Oral insulin: proof of concept in type 2 diabetic patients. Diabetes [Suppl 1] 52: A37
Kapitza C, Hompesch M, Scharling B et al. (2004) Intrasubject variability of inhaled insulin in type 1 diabetes: a comparison with subcutaneous insulin. Diabetes Technol Ther 6: 466–472
Kipnes M, Dandona P, Tripathy D et al. (2003) Control of postprandial glucose by an oral insulin product (HIM2) in patients with type 2 diabetes. Diabetes Care 26: 421–426
Koro CE, Bowlin SJ, Bourgeois N et al. (2004) Glycemic control 1988 to 2000 among U.S. adults diagnosed with type 2 diabetes: a preliminary report. Diabetes Care 27: 17–20
Lee DM (1992) Wie schmerzhaft ist die intensive Insulintherapie? Z Gesamt Inn Med 47: 266–269
Mather LE, Clauson P, Uy C et al. (2002) Pharmacokinetics and pharmacodynamics of pulmonary insulin using the AERx insulin diabetes management system during and after an upper respiratory tract infection. An open labelled crossover study in healthy subjects. Diabetologia [Suppl 2] 45: A261
Patton JS, Bukar J, Nagarajan S (1999) Inhaled insulin. Adv Drug Deliv Rev 35: 235–247
Perera AD, Kapitza C, Nosek L et al. (2002) Absorption and metabolic effect of inhaled insulin: intrapatient variability after inhalation via the aerodose insulin inhaler in patients with type 2 diabetes. Diabetes Care 25: 2276–2281
Pfützner A, Heise T, Steiner S et al. (2000) Inhaled technosphere/insulin shows a low variability in metabolic action in type 2 diabetic patients. Diabetes [Suppl 1] 49: A121
Rave K, Bott S, Heinemann L et al. (2005) Time-action profile of inhaled insulin in comparison with subcutaneously injected insulin lispro and regular human insulin. Diabetes Care 28: 1077–1082
Rosenstock J, Cappelleri JC, Bolinder B et al. (2004) Patient satisfaction and glycemic control after 1 year with inhaled insulin (Exubera) in patients with type 1 or type 2 diabetes. Diabetes Care 27: 1318–1323
Saudek CD (1993) Future developments in insulin delivery systems. Diabetes Care [Suppl 3] 16: 122–132
Skyler JS, Cefalu WT, Kourides IA et al. (2001) Efficacy of inhaled human insulin in type 1 diabetes mellitus: a randomised proof-of-concept study. Lancet 357: 331–335
Skyler JS, Weinstock RS, Raskin P et al. (2005) Use of inhaled insulin in a basal/bolus insulin regimen in type 1 diabetic subjects: a 6-month, randomized, comparative trial. Diabetes Care 28: 1630–1635
Wall DA (1995) Pulmonary absorption of peptides and proteins. Drug Delivery 2: 1–20
Weiss SR, Cheng SL, Kourides IA et al. (2003) Inhaled insulin provides improved glycemic control in patients with type 2 diabetes mellitus inadequately controlled with oral agents: a randomized controlled trial. Arch Intern Med 163: 2277–2282
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Arnolds, S., Heise, T. Neue Formen der Insulinapplikation. Diabetologe 2, 332–339 (2006). https://doi.org/10.1007/s11428-006-0062-6
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DOI: https://doi.org/10.1007/s11428-006-0062-6