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-peptide-negative type 1 diabetic
patients were studied on four occasions during 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 subsequent occasions, they received either an SC injection
of ultralente (0.3 U/kg) or CSII (0.3 U x kg(-1) x 24 h(-1)) (random sequence, crossover
design). After SC insulin injection or CSII, intravenous (IV) insulin was tapered,
and glucose was infused to clamp plasma glucose at 130 mg/dl for 24 h. Onset of action
(defined as reduction of IV insulin >50%) was earlier with NPH (0.8 +/- 0.2 h), CSII
(0.5 +/- 0.1 h), and ultralente (1 +/- 0.2 h) versus glargine (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 ultralente (20 +/- 6 h). NPH and ultralente exhibited a peak
concentration and action (at 4.5 +/- 0.5 and 10.1 +/- 1 h, respectively) followed
by waning, whereas glargine had no peak but had a flat concentration/action profile
mimicking CSII. Interindividual variability (calculated as differences in SD of plasma
insulin concentrations and glucose infusion rates in different treatments) 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 intersubject variability is also greater than
that of NPH. Glargine is a peakless insulin, it lasts nearly 24 h, it has lower intersubject
variability than NPH and ultralente, and it closely mimics CSII, the gold standard
of basal insulin replacement.