Comparison of pharmacokinetics and dynamics of the long-acting insulin analogs glargine and detemir at steady state in type 1 diabetes: a double-blind, randomized, crossover study.
OBJECTIVE
To compare pharmacokinetics and pharmacodynamics of insulin analogs glargine and detemir, 24 subjects with type 1 diabetes (aged 38 +/- 10 years, BMI 22.4 +/- 1.6 kg/m2, and A1C 7.2 +/- 0.7%) were studied after a 2-week treatment with either glargine or detemir once daily (randomized, double-blind, crossover study).


METHODS
Plasma glucose was clamped at 100 mg/dl for 24 h after subcutaneous injection of 0.35 unit/kg. The primary end point was end of action (time at which plasma glucose was >150 mg/dl).


RESULTS
With glargine, plasma glucose remained at 103 +/- 3.6 mg/dl up to 24 h, and all subjects completed the study. Plasma glucose increased progressively after 16 h with detemir, and only eight subjects (33%) completed the study with plasma glucose <180 mg/dl. Glucose infusion rate (GIR) was similar with detemir and glargine for 12 h, after which it decreased more rapidly with detemir (P < 0.001). Estimated total insulin activity (GIR area under the curve [AUC](0-end of GIR)) was 1,412 +/- 662 and 915 +/- 225 mg/kg (glargine vs. detemir, P < 0.05), with median time of end of action at 24 and 17.5 h (glargine vs. detemir, P < 0.001). The antilipolytic action of detemir was lower than that of glargine (AUC free fatty acids(0-24 h) 11 +/- 1.7 vs. 8 +/- 2.8 mmol/l, respectively, P < 0.001).


CONCLUSIONS
Detemir has effects similar to those of glargine during the initial 12 h after administration, but effects are lower during 12-24 h.
Porcellati
Francesca
F
Department of Internal Medicine, Section of Internal Medicine, Endocrinology and Metabolism, University of Perugia, Via E. Dal Pozzo, 06126 Perugia, Italy.
Rossetti
Paolo
P
Busciantella
Natalia Ricci
NR
Marzotti
Stefania
S
Lucidi
Paola
P
Luzio
Steven
S
Owens
David R
DR
Bolli
Geremia B
GB
Fanelli
Carmine G
CG
D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D007328:Insulin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069057:Insulin Detemir; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine; D000069057:Insulin Detemir