A Direct Comparison of Insulin Aspart and Insulin Lispro in Patients With Type 1 Diabetes

Plank, Johannes MD
Wutte, Andrea MSC
Brunner, Gernot MD
Siebenhofer, Andrea MD
Semlitsch, Barbara RN
Sommer, Romana MD
Hirschberger, Sabine MD
Pieber, Thomas R. MD

From ¹Diabetes und Metabolism, Department of Internal Medicine, Karl-Franzens University of Graz, Graz, Austria; and ²Novo Nordisk Pharma, Mainz, Germany.

Address correspondence and reprint requests to Johannes Plank, Department of Internal Medicine, Karl-Franzens University, Auenbruggerplatz 15, 8036 Graz, Austria. E-mail: [email protected].

Received for publication 17 May 2002 and accepted in revised form 21 July 2002.

T.R.P. is a paid consultant of Novo Nordisk Pharma and Lilly.

Abbreviations: AUC_ins, area under the curve for insulin; C_max, maximum baseline-corrected concentration; Exc_glu, blood glucose excursion; t_{50%decrease(ins)}, time to decrease to 50% of maximum insulin concentration; t_{50% of peak(ins)}, time to half-maximum insulin concentration; t_peak(ins), time to maximal insulin concentration.

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

Diabetes Care 25(11):p 2053-2057, November 2002.

OBJECTIVE

Both rapid-acting insulin analogs, insulin aspart and lispro, attenuate prandial glucose excursion compared with human soluble insulin. This trial was performed to study the pharmacokinetic and pharmacodynamic profiles of insulin aspart and insulin lispro in type 1 diabetic patients in a direct comparison and to investigate whether the administration of one analog results in favorable effects on prandial blood glucose control.

RESEARCH DESIGN AND METHODS

A total of 24 type 1 diabetic patients (age 36 ± 8 years, 16 men and 8 women, BMI 24.3 ± 2.6 kg/m², diabetes duration 17 ± 11 years, HbA_1c 7.9 ± 0.8%) on intensified insulin therapy were recruited into a single-center, randomized, double-blind, two-period, cross-over, glucose clamp trial. The subjects were given an individual need-derived dose of prandial insulin lispro or aspart immediately before a standard mixed meal.

RESULTS

With respect to blood glucose excursions from time 0 to 6 h (Exc_{glu(0-6 h)}) and from time 0 to 4 h (Exc_{glu(0-4 h)}), the pharmacodynamic effect of insulin aspart and insulin lispro can be declared equivalent. This was supported by comparison with maximum postprandial blood glucose excursions (C_max(glu)) (estimated ratio aspart/lispro ANOVA [90% CI]: 0.95 [0.80-1.13], 0.97 [0.82-1.17], and 1.01 [0.95-1.07] for Exc_{glu(0-6 h)}, Exc_{glu(0-4 h)}, and C_max(glu), respectively). For pharmacokinetic end points (maximum postprandial insulin excursions and area under the curve for insulin from time 0 to 6 h and from time 0 to 4 h), equivalence was indicated. No difference concerning absorption or elimination for time to maximal insulin concentration, time to half-maximum insulin concentration, and time to decrease to 50% of maximum insulin concentration was observed.

CONCLUSIONS

These data suggest that in type 1 diabetic patients, both insulin analogs are equally effective for control of postprandial blood glucose excursions.