OBJECTIVE To obtain clinically applicable data on the effects of regular human insulin and the Lys_B28, Pro_B29-human insulin analogue (lispro) on the correction of incidental hyperglycemia.

RESEARCH DESIGN AND METHODS The insulins were compared in a non-clamped randomized crossover study of 27 male IDDM patients. Hyperglycemia was induced by the withdrawal of the normal evening dose of insulin; the next morning patients fasted and received a single dose of study insulin according to a dosing nomogram. Blood glucose concentration and G_R (a measure of glucose corrected for differences in administered insulin dose: G_R = glucose concentration × BMI × insulin dose⁻¹) were followed for 4 h.

RESULTS The time courses of blood glucose concentration and G_R were significantly different after regular insulin in comparison with lispro (multiple analysis of variance, P < 0.001). At t = 120 min, glucose concentrations had decreased 1.4 mmol/l more with lispro than with regular insulin (95% confidence interval [CI] 0.6–2.3, P = 0.002). Similarly, G_R had decreased 4.4 mol · kg · IU⁻¹ · m⁻⁵ more with lispro than with regular insulin (95% CI 2.6–6.2, P < 0.001). The overall difference in glucose values was 0.87 mmol/l (lispro < regular insulin, P = 0.036), and the overall difference in G_R values was 1.96 mol · kg · IU⁻¹ · m⁻⁵ (lispro < regular insulin, P = NS). Unexpectedly, the intrinsic variability of G_R was higher for lispro than for regular insulin.

CONCLUSIONS The more rapid action of lispro is an advantage in the correction of hyperglycemia, even though actual differences in glucose concentrations are smaller than suggested by previous clamped studies.