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Exp Clin Endocrinol Diabetes 2005; 113(8): 435-443
DOI: 10.1055/s-2005-865806
Article

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

Insulin Glulisine, a New Rapid-Acting Insulin Analogue, Displays a Rapid Time-Action Profile in Obese Non-Diabetic Subjects

R. H. A. Becker1 , A. D. Frick1 , F. Burger2 , J. H. Potgieter2 , H. Scholtz2
  • 1Aventis Pharma Deutschland GmbH, Industriepark Höchst, Frankfurt am Main, Germany
  • 2FARMOVS-PAREXEL, Bloemfontein, Republic of South Africa
Further Information

Publication History

Received: December 15, 2004 First decision: April 13, 2005

Accepted: June 13, 2005

Publication Date:
08 September 2005 (online)

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Abstract

Aims/hypothesis: This study compared the pharmacokinetics and pharmacodynamics of insulin glulisine, insulin lispro, and regular human insulin in obese subjects. Methods: In this single-dose, randomized, double-blind, crossover euglycaemic clamp study, 18 non-diabetic subjects (mean body mass index [BMI] 34.7 kg · m-2) were randomized to receive subcutaneous injections of each insulin (0.3 U · kg-1) in pre-determined sequences. Results: Insulin glulisine and insulin lispro had more rapid-acting profiles than regular human insulin. Fractional glucose infusion rate (GIR)-area under curves (AUC) of the GIR curve and maximum GIR were greater for insulin glulisine and insulin lispro versus regular human insulin. Total glucose disposal was slightly greater with insulin glulisine than with regular human insulin, and was comparable to insulin lispro, although it decreased with increasing insulin resistance (HOMA index) with all insulins. Time to 20 % (early glucose disposal) and 80 % (bulk of activity) of total GIR-AUC were shorter for insulin glulisine and insulin lispro versus regular human insulin. This was corroborated by more rapid and shorter residing pharmacokinetic profiles of insulin glulisine and insulin lispro versus regular human insulin, evidenced by shorter times to 20 % of total INS-AUC, INS-Cmax (INS-tmax), and mean residence time. Moreover, time to 20 % of total GIR-AUC demonstrated a less rapid-acting profile for insulin lispro versus insulin glulisine, which was consistent with the slightly less rapid pharmacokinetic profile of insulin lispro. There was no significant correlation between BMI or subcutaneous fat thickness and pharmacokinetic or pharmacodynamic profiles for insulin glulisine, unlike insulin lispro and regular human insulin. Conclusions/interpretation: Insulin glulisine and insulin lispro demonstrated substantially more rapid time-action profiles than regular human insulin in obese non-diabetic subjects, which prevailed with insulin glulisine irrespective of BMI and subcutaneous fat thickness.

Key words

Obesity - insulin analogues - pharmacokinetics - pharmacodynamics

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1 Preliminary data by [Heise et al. (2005)] employing a BIOSTATOR supported clamp technique are affirmative.

R. H. A. Becker

Aventis Pharma Deutschland GmbH

Industriepark Höchst

65926 Frankfurt am Main

Germany

Phone: + 49(0)693054275

Fax: + 49 (0) 69 30 58 04 80

Email: Reinhard.Becker@sanofi-aventis.com