Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro

To compare the pharmacokinetics/dynamics of the long-acting insulin analog glargine with NPH, ultralente, and continuous subcutaneous (SC) infusion of insulin lispro (continuous subcutaneous insulin infusion [CSII]), 20 C-pep tide-negative type 1 diabetic patients mere studied on four occasions durin g an isoglycemic 24-h clamp. Patients received SC injection of either 0.3 U /kg glargine or NPH insulin (random sequence, crossover design). On two sub sequent occasions, they received either an SC injection of ultralente (0.3 U/kg) or CSII (0.3 U.kg(-1).24 h(-1)) (random sequence, crossover design). After SC insulin injection or CSII, intravenous (IV) insulin was tapered, a nd glucose was infused to clamp plasma glucose at 130 mg/dl for 24 h. Onset of action (defined as reduction of TV insulin >50%) was earlier with NPH ( 0.8 +/- 0.2 h), CSII (0.5 +/- 0.1 h), and ultralente (1 +/- 0.2 h) versus g largine (1,5 +/- 0.3 h) (P < 0.05) (mean +/- SE). End of action (defined as an increase in plasma glucose >150 mg/dl) occurred later with glargine (22 +/- 4 h) than with NPH (14 +/- 3 h) (P < 0.05) but was similar with ultral ente (20 +/- 6 h). NPH and ultralente exhibited a peak concentration and ac tion (at 4.5 +/- 0.5 and 10.1 +/- 1 h, respectively) followed by waning, wh ereas glargine had no peak but had a fiat concentration/action profile mimi cking CSII. Interindividual variability (calculated as differences in SD of plasma insulin concentrations and glucose infusion rates in different trea tments) was lower with glargine than with NPH and ultralente (P < 0.05) but was similar with glargine and CSII (NS). In conclusion, NPH and ultralente are both peak insulins. Duration of action of ultralente is greater, but i ntersubject variability is also greater than that of NPH. Glargine is a pea kless insulin, it lasts nearly 24 h, it has lower intersubject variability than NPH and ultralente, and it closely mimics CSII, the gold standard of b asal insulin replacement.