Subscribe to RSS
DOI: 10.1055/s-2001-14106
Klinische Wirkungen und Pharmakodynamik der Insulinanaloga Lispro, Aspart und Glargin
Clinical efficacy and pharmacodynamics of the insulin analogs lispro, aspart and glarginPublication History
Publication Date:
31 December 2001 (online)
![](https://www.thieme-connect.de/media/dmw/200120/lookinside/thumbnails/10.1055-s-2001-14106-1.jpg)
Subkutane Injektion der bisher üblichen Insulinpräparationen ermöglicht keine optimale Imitation des endogenen Insulinsekretionsmusters, da subkutan injiziertes Normalinsulin einen zu langsamen Wirkbeginn und eine zu lange Wirkdauer (bis zu 12 h bei Verwendung hoher Dosen) aufweist [Abb. 1] [30]. Das als Verzögerungsinsulin verwendete NPH-Insulin weist nicht den gewünschten niedrigen und konstanten metabolischen Effekt über die Zeit auf, sondern eine ausgeprägte maximale Wirkung nach ca. 6 h, mit einem konstanten Absinken der Wirkung in der Zeit danach [Abb. 1] [36]. Unter anderem deshalb gelingt es vielen Diabetes-Patienten nicht, eine gute Stoffwechselkontrolle zu etablieren [5] [7] [9] .
Literatur
- 1 Anderson J H, Brunelle R L, Keohane P. et al . Mealtime treatment with insulin analogue improves postprandial hyperglycemia and hypoglycemia in NIDDM patients. Arch Intern Med. 1997; 157 1249-1255
- 2 Anderson J H, Brunelle R L, Koivisto V. et al . Improved mealtime treatment of diabetes mellitus using insulin analogue. Clin Ther. 1997; 19 62-72
- 3 Anderson J H, Brunelle R L, Koivisto V A, Pfützner A, Trautmann M E, Vignati L, DiMarchi R. and the Multicenter Insulin Lispro Study Group . Reduction of postprandial hyperglycemia and frequency of hypoglycemia in IDDM patients on insulin-analog treatment. Diabetes. 1997; 46 265-270
- 4 Bahr M, Kolter T, Seipke G, Eckel J. Growth promoting and metabolic activity of the human insulin analogue [GlyA21,ArgB31,ArgB32]insulin (HOE 901) in muscle cells. Eur J Pharmacol. 1997; 320 259-265
- 5 Berger M. Towards more physiological insulin therapy in the 1990 s. A comment. Diabetes Res Clin Pract. 1989; 6 S25-S31
- 6 Berger M. Safety of insulin glargine. Lancet. 2000; 356 2013-2014
- 7 Berger M, Heinemann L. Are presently available insulin analogues clinically beneficial?. Diabetologia. 1997; 40 S91-S96 (Suppl 2))
- 8 Berti L, Kellerer M, Bossenmaier B, Seffer E, Seipke G, Haring H U. The long acting human insulin analog HOE 901: characteristics of insulin signalling in comparison to Asp(B10) and regular insulin. Horm Metab Res. 1998; 30 123-129
- 9 Bolli G B, Di Marchi R D, Park G D, Pramming S, Koivisto V A. Insulin analogues and their potential in the management of diabetes mellitus. Diabetologia. 1999; 42 1151-1167,
- 10 Bolli G B, Owens D R. Insulin glargine. Lancet. 2000; 356 443-445
- 11 Bott S, Bott U, Berger M, Mühlhauser I. Intensified insulin therapy and the risk of severe hypoglycaemia. Diabetologia. 1997; 40 926-932
- 12 Bott U, Ebrahim S, Hirschberger S, Leukel P, Sieber H J. Effect of the insulin analogue insulin aspart on quality-of-life and treatment satisfaction in type 1 diabetic patients. Diabetologia. 1999; 42 A237 (Suppl 1)
- 13 Bott U, Mühlhauser I, Overmann H, Berger M. Validation of a diabetic-specific quality-of-life scale for patients with type 1 diabetes. Diabetes Care. 1998; 21 757-769
- 14 Brange J, Owens D R, Kang S, Volund A. Monomeric insulins and their experimental and clinical implications. Diabetes Care. 1990; 13 923-954
- 15 Brange J, Ribel U, Hansen J F, Dodson G, Hansen M T, Havelund S, Melberg S G, Norris F, Norris K, Snel L. et al . Monomeric insulins obtained by protein engineering and their medical implications. Nature. 1988; 333 679-682
- 16 Brunelle R L, Llewelyn J, Anderson J H, Gale E A, Koivisto V. Meta-analysis of the effect of insulin lispro on severe hypoglycemia in patients with type 1 diabetes. Diabetes Care. 1998; 21 1726-1731
- 17 Brunner G A, Hirschberger S, Sendlhofer G. et al . Post-prandial administration of the insulin analogue insulin aspart in patients with Type 1 diabetes mellitus. Diabet Med. 2000; 17 371-375
- 18 Chantelau E. Evidence that upregulation of serum IGF-1 concentration can trigger acceleration of diabetic retinopathy. Br J Ophthalmol. 1998; 82 725-730
- 19 Chantelau E, Kohner E M. Why some cases of retinopathy worsen when diabetic control improves. BMJ. 1997; 315 1105-1106
- 20 Ciofetta M, Lalli C, Del S indaco P. et al . Contribution of postprandial versus interprandial blood glucose to HbA1c in type 1 diabetes on physiologic intensive therapy with lispro insulin at mealtime. Diabetes Care. 1999; 22 795-800
- 21 Colombel A, Murat A, Krempf M, Kuchly-Anton B, Charbonnel B. Improvement of blood glucose control in type 1 diabetic patients treated with lispro and multipe NPH injections. Diabetic Med. 1999; 16 319-324
- 22 Ebeling P, Jansson P A, Smith U, Lalli C, Bolli G, Koivisto V. Strategies toward improved control during insulin lispro therapy in IDDM. Diabetes Care. 1997; 20 1287-1289
- 23 Gale E A. The UK Trial Group . A randomized, controlled trial comparing insulin lispro with human soluble insulin in patients with Type 1 diabetes on intensified insulin therapy. Diabet Med. 2000; 17 209-214
- 24 Garg S K, Carmain J A, Braddy K C, Anderson J H, Vignati L, Jennings M K, Chase H P. Pre-meal insulin analogue insulin lispro vs. Humulin R insulin treatment in young subjects with type 1 diabetes. Diabetic Med. 1996; 13 47-52
- 25 G lazer N B, Zalani S, Anderson J H, Bastyr E J. Safety of insulin lispro: pooled data from clinical trials. Am J Health Syst Pharm. 1999; 56 542-547
- 26 Hanaire-Broutin H, Melki V, Bessieres-Lacombe S, Tauber J P. The Study Group for the Development of Pump Therapy in Diabetes . Comparison of continuous subcutaneous insulin infusion and multiple daily injection regimens using insulin lispro in type 1 diabetic patients on intensified treatment: a randomized study. Diabetes Care. 2000; 23 1232-1235
- 27 Hansen B F, Danielsen G, Drejer K, Sorensen A R, Wiberg F C, Klein H H, Lundemose A G. Sustained signalling from the insulin receptor after stimulation with insulin analogues exhibiting increased mitogenic potency. Biochem J. 1996; 315 271-279
- 28 Heinemann L. Hypoglycemia and insulin analogues: is there a reduction in the incidence?. J Diabetes Complications. 1999; 13 105-114
- 29 Heinemann L, Breuer J, Cebulla D, Wüssel B, Bender R, Heise T. Wirkungsprofile von Normalinsulin, NPH-Insulin sowie einer 25/75-Mischung hergestellt aus gentechnologischem bzw. semisynthetischem Humaninsulin. Diabetes u Stoffw. 1996; 5 157-163
- 30 Heinemann L, Heise T, Jorgensen L N, Starke A AR. Action profile of the rapid acting insulin analogue B28Asp. Diabetic Med. 1993; 10 535-539
- 31 Heinemann L, Heise T, Wahl C h, Trautmann M E, Ampudia J, Starke A AR, Berger M. Prandial glycaemia after a carbohydrate-rich meal in type I diabetic patients using the rapid acting insulin analogue [Lys(B28), Pro(B29)]. Diabetic Med. 1996; 13 625-629
- 32 Heinemann L, Kapitza C, Starke A AR, Heise T. Time-action profile of the insulin analogue B28Asp. Diabetic Med. 1996; 13 683-684
- 33 Heinemann L, Linkeschova R, Rave K, Hompesch B, Sedlak M, Heise T. Time-action profile of the long-acting insulin analog insulin glargine (HOE901) in comparison with those of NPH insulin and placebo. Diabetes Care. 2000; 23 644-649
- 34 Heinemann L, Weyer C, Rauhaus M, Heinrichs J, Heise T. Variability of the metabolic effect of soluble insulin and the rapid acting insulin analogue insulin aspart. Diabetes Care. 1998; 21 1910-1914
- 35 Heise T, Bott S, Rave K, Dressler A, Rosskamp R, Heinemann L. No evidence for accumulation of HOE901 after multiple injections in type 1 diabetic patients. Diabetologia. 2000; 43 A196 (Suppl 1)
- 36 Heise T, Weyer C, Serwas A, Heinrichs J, Osinga J, Roach P, Woodworth J R, Gudat U, Heinemann L. Time-action profiles of novel premixed preparations of insulin lispro and NPL insulin. Diabetes Care. 1998; 21 800-803
- 37 Heller S R, Amiel S A, Mansell P. U.K. Lispro Study Group . Effect of the fast-acting insulin analog lispro on the risk of nocturnal hypoglycemia during intensified insulin therapy. Diabetes Care. 1999; 22 1607-1611
- 38 Holleman F, Schmitt H, Rottiers R, Rees A, Symanowski S, Anderson J, . The Benelux-UK insulin lispro study group . Reduced frequency of severe hypoglycemia and coma in well-controlled IDDM patients treated with insulin lispro. Diabetes Care. 1997; 20 1827-1832
- 39 Home P D. Rapid-acting insulin analogues: when randomized clinical trial results do not help. Diabet Med. 2000; 17 6-8 (Suppl 2)
- 40 Home P D, Lindholm A, Hylleberg B, Round P, . for the U.K.Insulin Aspart Study Group . Improved glycemic control with insulin aspart. Diabetes Care. 1998; 21 1904-1909
- 41 Home P D, Lindholm A, Riis A. Insulin aspart vs. human insulin in the management of long-term blood glucose control in Type 1 diabetes mellitus: a randomized controlled trial. Diabetic Med. 2000; 17 762-770
- 42 Jorgensen L N, Dideriksen L H. Preclinical studies of rapid-acting insulin analogues. Thieme Verlag In: Frontiers in Insulin Pharmacology, Berger M, Gries FA (eds) 1993: 110-117
- 43 Jörgens V, Grüsser M, Bott U, Mühlhauser I, Berger M. Effective and safe translation of intensified insulin therapy to general internal medicine departments. Diabetologia. 1993; 36 99-105
- 44 Kang S, Brange J, Burch A, Volund A, Owens D R. Subcutaneous insulin absorption explained by insulin’s physicochemical properties. Evidence from absorption studies of soluble human insulin and insulin analogues in humans. Diabetes Care. 1991; 14 942-948
- 45 Kellerer M, Häring H U. Insulin analogues: impact of cell model characteristics on results and conclusions regarding mitogenic properties. Exp Clin Endocrinol Diabetes. 2001; 109 63-64
- 46 Kotsanos J G, Vignati L, Huster W. et al . Health-related quality-of-life results from multinational clinical trials of insulin lispro. Diabetes Care. 1997; 20 948-958
- 47 Kurtzhals P, Schaffer L, Sorensen A, Kristensen C, Jonassen I, Schmid C, Trub T. Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes. 2000; 49 999-1005
- 48 Lalli C, Ciofetta M, Del Sindaco P. et al . Long-term intensive treatment of type 1 diabetes with the short-acting insulin analogue lispro in variable combination with NPH insulin at mealtime. Diabetes Care. 1999; 22 468-477
- 49 Lepore M, Pampanelli S, Fanelli C. et al . Pharmacokinetics and pharmacodynamics of subcutaneous injection of long- acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes. 2000; 49 2142-2148
- 50 Lindholm A , Andersen H F, Hylleberg B , Gall M A. A review of the safety profile of insulin aspart. Diabetologia. 2000; 43 (Suppl 1) A199
- 51 Melki V, Renard E, Lassmann V ague V. et al . Improvement of HbA1c and blood glucose stability in IDDM patients treated with lispro insulin analog in external pumps. Diabetes Care. 1998; 21 977-982
- 52 Nathan D N. Long-term complications of diabetes mellitus. N Engl J Med. 1993; 328 1676-1685
- 53 Pampanelli S, Torlone E, Lalli C. et al . Improved postprandial metabolic control after subcutaneous injection of a short acting insulin analog in IDDM of short duration with residual pancreatic-cell function. Diabetes Care. 1995; 18 1452-1459
- 54 Pieber T R, Eugene-Jolchine I, Derobert E, . the European Study Group of HOE901 in Type 1 diabetes . Efficacy and safety of HOE901 versus NPH insulin in patients with type 1 diabetes. Diabetes Care. 2000; 23 157-162
- 55 Raskin P, Guthrie R A, Leiter L, Riis A, Jovanovic L. Use of insulin aspart, a fast-acting insulin analog, as the mealtime insulin in the management of patients with type 1 diabetes. Diabetes Care. 2000; 23 583-588
- 56 Raskin P, Klaff L, Bergenstal R, Halle J P, Donley D, Mecca T. A 16-week comparison of the novel insulin analog insulin glargine (HOE 901) and NPH human insulin used with insulin lispro in patients with type 1 diabetes. Diabetes Care. 2000; 23 1666-1671
- 57 Ratner R E, Hirsch I B, Neifing J L, Garg S K, Mecca T E, Wilson C A. U.S. Study Group of Insulin Glargine in Type 1 Diabetes . Less hypoglycemia with insulin glargine in intensive insulin therapy for type 1 diabetes. Diabetes Care. 2000; 23 639-643
- 58 Rave K, Sawicki P T, Heise T, Heinemann L. Pharmacodynamic properties of insulin in patients with and without diabetic nephropathy. Diabetes. 2000; 49 A76
- 59 Renner R, Pfutzner A, Trautmann M, Harzer O, Sauter K, Landgraf R. German Humalog-CSII Study Group . Use of insulin lispro in continuous subcutaneous insulin infusion treatment. Results of a multicenter trial. Diabetes Care. 1999; 22 784-788
- 60 Reviriego J, Millan M. Health-related quality of life and insulin lispro. A naturalistic approach. Diabetes Care. 1998; 21 1203-1204
- 61 Rosenstock J, Park G, Zimmerman J. U.S. Insulin Glargine (HOE 901) Type 1 Diabetes Investigator Group . Basal insulin glargine (HOE 901) versus NPH insulin in patients with type 1 diabetes on multiple daily insulin regimens. Diabetes Care. 2000; 23 1137-1142
- 62 Rowe R, Anderson J H, Gale E. A double-blind comparison of insulin lispro and regular insulin in patients on a multiple injection regimen. Diabetes. 1996; 45 71A (Suppl 2)
- 63 Schmitt H, Symanowski S M, Holleman F, Rees A, Rottiers R, Anderson J H. Comparison of pre-meal therapy with insulin lispo and regular insulin in patients with IDDM. Diabetologia. 1996; 39 A221 (Suppl 1)
- 64 Scholtz H E, van Niekerk N, Meyer B H, Rosenkranz B. An assessment of the variability in the pharmacodynamics (glucose lowering effect) of HOE901 compared to NPH and ultralente human insulins using the euglycaemic clamp technique. Diabetologia. 1999; 42 A235 (Suppl 1)
- 65 UK Prospective Diabetes Study Group . Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998; 352 837-853
- 66 Yki-Jarvinen H, Dressler A, Ziemen M. HOE 901/3002 Study Group . Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. Diabetes Care. 2000; 23 1130-1136
- 67 Zinman B, Tildesly H, Chiasson J L, Tsui E, Strack T. Insulin lispro in CSII: results of a double-blind cross-over study. Diabetes. 1997; 46 440-443
Korrespondenz
PD Dr. Lutz Heinemann
Profil Institut für Stoffwechselforschung
GmbH
Stresemannallee 6
41460 Neuss
Phone: 02131/155402
Fax: 02131/155 409
Email: Lutz.Heinemann@profil-research.de