No evidence for accumulation of insulin glargine (LANTUS): a multiple injection study in patients with Type 1 diabetes.
OBJECTIVE
Insulin glargine is a long-acting insulin analogue that is metabolically active for at least 24 h. We investigated the multiple-dose pharmacokinetic properties of insulin glargine to determine whether daily injections lead to the accumulation of circulating insulin levels and a corresponding decrease in blood glucose levels in patients with Type 1 diabetes.


METHODS
Fifteen patients using preprandial insulin lispro (mean age 36 +/- 9 years, body mass index 24.6 +/- 2.2 kg/m(2)) completed the study. Each patient's optimal insulin glargine dose was determined during a dose-finding phase. After a washout period, patients were treated over 12 days with a constant daily dose of insulin glargine injected in the abdominal subcutaneous adipose tissue at 22:00 h, and with preprandial insulin lispro. Free serum insulin (FSI) and blood glucose concentrations were assessed hourly after the first, fourth, and eleventh injection, after which patients fasted for 24 h and did not use any other insulin preparation.


RESULTS
There were no changes in daily insulin doses during the dose-finding phase (insulin glargine: initial dose 24 +/- 6 IU, mean change 0 +/- 3 IU; insulin lispro: 18 +/- 9 IU, 0 +/- 7 IU). The time course of FSI was comparable on the three pharmacokinetic study days. Notably, the trough FSI at the end of the sampling periods was almost identical (day 1, 79 +/- 56 pmol/l, day 4, 77 +/- 56 pmol/l, day 11, 86 +/- 60 pmol/l). No changes occurred in any of the pharmacokinetic parameters studied.


CONCLUSIONS
There is no evidence that insulin glargine accumulates after multiple injections over 12 days. These results indicate that the predetermined dose of insulin glargine will not need to be reduced after commencing treatment because of a risk of accumulation.
Heise
T
T
Profil Institute for Metabolic Research, Neuss Germany. tim.hise@profil-research.de
Bott
S
S
Rave
K
K
Dressler
A
A
Rosskamp
R
R
Heinemann
L
L
D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D000069036:Insulin Glargine; D061268:Insulin Lispro; D049528:Insulin, Long-Acting; D008657:Metabolic Clearance Rate; D013997:Time Factors
D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine