Exp Clin Endocrinol Diabetes 2006; 114(9): 511-519
DOI: 10.1055/s-2006-924424

© J. A. Barth Verlag in Georg Thieme Verlag KG · Stuttgart · New York

Biphasic Insulin Aspart Given Thrice Daily is as Efficacious as a Basal-Bolus Insulin Regimen with Four Daily Injections

A Randomised Open-Label Parallel Group Four Months Comparison in Patients with Type 2 DiabetesR. J. Ligthelm 1 , U. Mouritzen 2 , H. Lynggaard 2 , M. Landin-Olsson 3 , C. Fox 4 , C. le Devehat 5 , E. Romero 6 , A. Liebl 7
  • 1Havenziekenhuis, Rotterdam, The Netherlands
  • 2Novo Nordisk A/S, Bagsvasrd, Denmark
  • 3Universitetssjukhuset Lund, Lund, Sweden
  • 4Northampton General Hospital, Cliftonville, Northampton, United Kingdom
  • 5Hôpital Pierre Beregovoy, Nevers Cedex, France
  • 6Institute de Endocrinologia, UVA, Valladolid, Spain
  • 7Diabeteszentrum, Bad Heilbrunn, Germany
Further Information

Publication History

Received: January 3, 2006 First decision: May 3, 2006

Accepted: May 29, 2006

Publication Date:
17 November 2006 (online)


Aims: To show that a thrice daily meal-time biphasic insulin aspart (BIAsp) treatment regimen is as efficacious as a 4 times daily basal-bolus regimen with human isophane insulin (NPH) and insulin aspart (IAsp). Methods: A multinational, randomised, open-label parallel-group trial in 394 patients with type 2 diabetes on a once or twice daily insulin regimen. Patients were randomised 1:1 to BIAsp or IAsp+NPH for 16 weeks. The BIAsp group was treated according to individual needs using BMI as a surrogate index of insulin resistance. Subjects administered BIAsp 70 (BMI≤30 kg/m2) or BIAsp 50 (BMI>30 kg/m2) with breakfast and lunch and BIAsp 30 with dinner. The IAsp+NPH group injected IAsp at meals and NPH at bedtime as basal insulin. HbAlc levels after 16 weeks were compared between treatments using a predefined non-inferiority criterion of 0.4%. The incidence of hypoglycaemic episodes and adverse events was evaluated. Results: Mean HbAlc (±SD) decreased from 9.1±0.7% to 7.8±1.0% with both treatments. Glycaemic control provided by BIAsp was non-inferior to that obtained by the IAsp+NPH (intention to treat ITT) population: diff, HbAlc -0.05%; 95% CI (-0.24; 0.14); per protocol (PP) population: diff, HbAlc -0.03%; 95% CI (-0.23; 0.16). Similar improvements in glycaemic control in both groups were confirmed by self-measured 8-point plasma glucose (PG) profiles, average and fasting PG concentrations, and average prandial PG increments. The incidence of adverse events and hypoglycaemic episodes was similar in the two treatment groups. Conclusions: A thrice daily meal-time BIAsp regimen is a suitable alternative to an intensified insulin regimen in people with inadequately controlled type 2 diabetes mellitus, and requires fewer daily injections than a basal-bolus therapy without compromising efficacy and safety.



Dr. Robert J. Ligthelm

Havenziekenhuis·Afd. Interne Geneeskunde

Haringvliet 2

3011 TD Rotterdam

The Netherlands

Phone: +3/11/04 04 33 00

Fax: +3/11/04 14 51 38

Email: rjligthelm@cistron.nl