Aim: Because of its zinc-free formulation insulin glulisine (GLU) might have a faster onset of action than other short-acting analogues. We compared the pharmacokinetics and pharmacodynamics of GLU with those of insulin aspart (ASP). Methods: Twelve healthy subjects, aged 18-65 years, participated in this randomized, double-blind, crossover trial. Subjects received 0.2 U/kg GLU or ASP under euglycaemic glucose-clamp conditions. Results: GLU showed a significantly higher early metabolic effect (area under the glucose infusion rate (GIR) curve in the first 30 min AUC-GIR(0-)30 down arrow min 30.3+/-26.4 vs. 16.2+/-18.4 mg/kg, P = 0.0421) than ASP, an earlier onset of action (time to 10% of GIR(max) (GIR(max)-t(10%)) 9 vs. 17 min, P = 0.0146) and a faster absorption (shorter times to 10% and 20% of INSmax, P = 0.0005 each). Conclusions: As demonstrated previously versus lispro, GLU, the only analogue formulated without zinc, also has an earlier onset of action than ASP.