Differences in Pharmacokinetics and Pharmacodynamics of Insulin Lispro and Aspart in Healthy Volunteers

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Abstract
Pharmacokinetic and pharmacodynamic profiles of the rapid-acting insulin analogues lispro and aspart were compared in a randomized, double-blind crossover study of 20 fasting healthy men following a single subcutaneous injection. Either insulin lispro or aspart, 0.05 U/kg-body-weight, was injected subcutaneously and followed by determination of 5-h profiles of plasma glucose, serum C-peptide and insulin concentrations. Lowest glucose concentrations were observed after 50 min in the aspart group (3.2 ± 0.1 mmol/l versus lispro 3.5 ± 0.1 mmol/l; p = 0.026) and after 60 min in the lispro group (3.4 ± 0.1 mmol/l). For blood glucose tmin was 59.3 ± 3.4 min in the aspart and 63.5 ± 5.3 min in the lispro group (ns). After 40 min a lower C-peptide was determined for aspart (225 ± 21 pmol/l versus lispro 309 ± 33 pmol/l; p = 0.031), whereas minimal C-peptide concentrations were reached in both groups after 105 min (lispro 117 ± 21 pmol/l versus aspart 105 ± 18 pmol/l). The maximal concentration of insulin was detected in both groups after 40 min (lispro 20.8 ± 1.1 mU/l versus aspart 24.6 ± 1.3 mU/l; p = 0.032). For insulin tmax was 33.0 ± 2.6 min in the aspart versus 33.3 ± 2.6 min in the lispro group (ns). The present results indicate a more rapid absorption of insulin aspart in comparison to insulin lispro. Higher insulin concentrations after subcutaneus injection may be advantageous in meal-related treatment of diabetes.

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