Pharmacokinetics and Pharmacodynamics of the Long-Acting Insulin Analog Glargine After 1 Week of Use Compared With Its First Administration in Subjects With Type 1 Diabetes

Abstract

Pharmacokinetics and pharmacodynamics of the long-acting insulin analog glargine (1) are superior to those of insulin NPH (2–9). In the clinical setting, this translates into lower risk of nocturnal hypoglycemia (10–13), lower A1C (provided that appropriate requirements of mealtime rapid-acting insulin are met) (11–13), and the convenience of once (12), compared with multiple, administration of NPH (14). However, no study has examined subjects after several days of its use versus the “first” subcutaneous injection. The present studies were undertaken to establish the pharmacokinetics and pharmacodynamics of insulin glargine in type 1 diabetes after 1 week of its once-daily use and to compare it with those observed after the first injection. After institutional review board approval, 20 type 1 diabetic subjects (12 male subjects, age 31 ± 2 years, type 1 diabetes duration 11 ± 1 years, BMI 23.3 ± 0.4 kg/m2, fasting plasma C-peptide <0.02 nmol/l, and A1C 7.1 ± 0.2%) using NPH as basal insulin and human regular insulin ( n = 7) or lispro insulin ( n = 13), in combination with NPH at each meal as previously described (14), were studied. During a 2-week run-in period, subjects continued their previous model of insulin therapy, i.e., human regular insulin or the rapid-acting insulin analog lispro at breakfast, lunch, and dinner and NPH insulin at bedtime, or even at each meal in those patients ( n = 13) who used lispro (14). Thereafter, subjects were studied with the glucose clamp technique after subcutaneous injection of 0.3 units/kg insulin glargine as previously described (6). Subjects …