The use of insulin analogues is rapidly expanding. At present, there are two short-acting analogues available for practical use, insulin aspart and insulin lispro, and one long-acting analogue, insulin glargine. Another long-acting analogue, insulin detemir, is still under development. The time action profile of short-acting analogues is both much more rapid and shorter than that of human insulin; the prominent feature of the long-acting analogues is their peakfree and fairly constant action. Insulin analogues offer alternative options for the whole spectrum of insulin therapy in type 1 and type 2 diabetes patients. The perception by many patients is strikingly positive, in particular regarding the overall quality of life. In objective efficacy terms, however, the potential to improve the degree of metabolic control appears to be only minor, yet demonstrable, provided the analogues are used according to their specific time action profile. This ensured, analogues are instrumental in minimizing the side effects of insulin therapy, i.e. the risk of (nocturnal) hypoglycaemia or problems with body weight control. Although there are no indications of safety concerns with insulin analogues, the availability of long-term outcome data based upon observations in human patients would be very valuable.

1.
The Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and the progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–986.
2.
Mehnert H, Standl E, Usadel KH (eds): Diabetologie in Klinik und Praxis. Stuttgart, New York, Thieme, 1999.
3.
Heinemann L, Heise T: Clinical efficacy and pharmacodynamics of the insulin analogs lispro, aspart and glargine. Dtsch Med Wschrift 2001;126:597–604.
4.
Heinemann L, Sinha K, Weyer C, Loftager M, Hirschberger S, Heise T: Time action profile of the soluble, fatty acid acylated, long-acting insulin analogue NN304. Diab Med 1999;16:332–338.
5.
Hillenbrand H, Nuber G, Standl E: Insulinanaloga: results of a survey. Diab J 2001;50:16–18.
6.
Bolli GB, Di Marchi RD, Park GD, Pramming S, Koivisto VA: Insulin analogues and their potential in the management of diabetes mellitus. Diabetologia 1999;42:1151–1167.
7.
Bruttomesso D, Pianta A, Mari A: Restauration of early rise in plasma insulin levels improves the glucose tolerance of type 2 diabetic patients. Diabetes 1999;48:99–105.
8.
Yki-Järvinen H: Comparisons of insulin regimens for patients with type 2 diabetes. Curr Op Endocrinol Diab 7:175–183.
9.
Home PD, Lindholm A, Hylleberg B, Round P and the UK Insulin Aspart Study Group: Improved glycemic control with insulin aspart: a multicenter randomized double-blind crossover trial in type 1diabetic patients. Diab Care 1998;21:1904–1909.
10.
Raskin P, Guthrie RA, 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. Diab Care 2000;23:583.
11.
Home PD, Linholm A, Riis A and the European Insulin Aspart Study Group: Insulin aspart vs human insulin in the management of long-term blood glucose control in Type 1 diabetes mellitus: a randomized controlled trial. Diab Med 2000;17:762–771.
12.
Heller S, Colagiuri S, Vaaler S, Wolfenbuttel BHR, Kölendorf C, Friberg P, Windfeld K, Lindholm A: Reduction of hypoglycemia with insulin aspart: a double blind randomized crossover trial in type 1 diabetes. Submitted.
13.
Melki V, Renard E, Lassmann-Vague V: Improvement of HbA1c and blood glucose stability in IDDM patients treated with lispro insulin analog in external pumps. Diab Care 1998;21:977–982.
14.
Renner R, Pfützner A, Trautmann M, Harzer O, Sauter K, Landgraf R: Use of insulin lispro in continuous subcutaneous insulin infusion treatment. Results of a multicenter trial. Diab Care 1999;22:784–788.
15.
Zinman B, Tildesley H, Chiasson JL, Tsui E, Strack T: Insulin lispro in CSII: results of a double- blind crossover study. Diabetes 1997;46:440–443.
16.
Ciofetta M, Lalli C, Del Sindaco P: Contribution of postprandial versus interprandial blood glucose to HbA1c in type 1 diabetes on physiologic intensive therapy with lispro insulin at mealtime. Diab Care 1999;22:795–800.
17.
Del Sindaco P, Ciofetta M, Lalli C: Use of the short- acting insulin analog lispro in intensive treatment of type 1 diabetes mellitus: importance of appropriate replacement of basal insulin and time-interval injection–meal. Diab Med 1998;15:592–600.
18.
Ebeling P, Jansson PA, Smith U, Lalli C, Bolli GB, Koivisto VA: Strategies toward improved control during insulin lispro therapy in IDDM. Importance of basal insulin. Diab Care 1997;20:1287–1289.
19.
Lalli C, Ciofetta M, Del Sindaco P: Longterm intensive treatment of type 1 diabetes with the short acting insulin analog lispro in variable combination with NPH insulin at mealtime. Diab Care 1999;22:468–477.
20.
Anderson JHJ, Brunelle RL, Koivisto VA: Reduction of postprandial hyperglycemia and frequency of hypoglycemia in IDDM patients on insulin – analog treatment. Multicenter Insulin Lispro Study Group. Diabetes 1997;46:265–270.
21.
Anderson JHJ, Brunelle RL, Keohane P: Mealtime treatment with insulin analog improves postprandial hyperglycemia and hypoglycemia in patients with non-insulin-dependent diabetes mellitus. Multicenter Insulin Lispro Study Group. Arch Intern Med 1997;157:1249–1255.
22.
Brunelle BL, Llewelyn J, Anderson JHJ, Gale EA, Koivisto VA: Meta-analysis of the effect of insulin lispro on severe hypoglycemia in patients with type I diabetes. Diab Care 1998;21:1726–1731.
23.
Gillies PS, Figgitt DP, Lamb HM: Insulin glargine. Drugs 2000;59:253–260.
24.
Pieber TR, Eugène-Jolchine I, Derobert E and the European Study Group of HOE 901 in Type 1 Diabetes: Efficacy and safety of Hoe 901 versus NPH insulin in patients with type 1 diabetes. Diab Care 2000;23:157–162.
25.
Ratner RE, Hirsch IB, Neifing JL, Garg SK, Mecca TE, Wilson CA: Less hypoglycemia with insulin glargine in intensive therapy for type 1 diabetes. Diab Care 2000;23:639–643.
26.
Rosenstock J, Park G, Zimmermann J: Basal insulin glargine (Hoe 901) versus NPH insulin in patients with type 1 diabetes on multiple daily insulin regimens. Diab Care 2000;23:1137–1142.
27.
Raskin P, Klaff L, Bergenstal R, Halle JP, Donley D, Mecca T: A 16-week comparison of the novel insulin analog glargine (Hoe 901) and NPH insulin used with insulin lispro in patients with type 1 diabetes. Diab Care 2000;23:1666–1671.
28.
Yki-Järvinen H, Dressler A, Ziemen M and the Hoe 901/3002 Study Group: Less nocturnal hypoglycemia and better postdinner glucose control with bedtime glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. Diab Care 2000;23:1130–1136.
29.
Rosenstock J, Schwartz S, Clark C: Efficacy and safety of Hoe 901 (insulin glargine) in subjects with type 2 diabetes mellitus: a 28-week randomised, NPH-insulin controlled trial. Diab Care 2001;24:631–636.
30.
Brunner GA, Sendhofer G, Wutte A: Pharmacokinetic and pharmacodynamic properties of long acting analog NN304 in comparison to NPH insulin in humans. Exp Clin Endocrinol Diab 2000;108:100–105.
31.
Hermansen K, Madsbad S, Perrild H, Kristensen A, Axelsen M: Comparison of the soluble basal insulin analog detemir with NPH insulin. A randomised open crossover trial in type1 diabetic subjects on basal- bolus therapy. Diab Care 2001;24:296–301.
32.
Roberts A, Standl E, Bayer T, Munksgaard E, Lang H: Efficacy and safety of 6-month treatment with insulin detemir in type 1 diabetic patients on a basal-bolus regimen. Diabetologia 2001;44 (suppl 1):A.
33.
Kurtzhals P, Schäffer L, Sørensen A, Kristensen C, Jonassen I, Schmid C, Trüb T: Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed to clinical use. Diabetes 2000;49:999–1005.
34.
Berti I, Kellerer M, Bossenmaier B, Seffer EE, Seipke G, Häring HU: The long acting human insulin analog Hoe 901:Characteristics of insulin signalling in comparison to Asp (B10) and regular insulin. Horm Metabol Res 1998;30:123–129.
35.
Glazer NB, Zalani S, Anderson JHJ, Bastyr EJ: Safety of insulin lispro: pooled data from clinical trials. Am J Health Syst Pharm 1999;56:542–547.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.