Comparison of pharmacokinetics and dynamics of the long-acting insulin analogs glargine and detemir at steady state in type 1 diabetes mellitus: a double-blind, randomized, cross-over study
- Francesca Porcellati, MD,
- Paolo Rossetti, MD,
- Natalia Ricci Busciantella, MD,
- Stefania Marzotti, MD,
- Paola Lucidi, MD,
- Steven Luzio, MD*,
- David R. Owens, MD*,
- Geremia B. Bolli, MD (gbolli{at}unipg.it) and
- Carmine G. Fanelli, MD
- Internal Medicine, Section of Internal Medicine, Endocrinology and Metabolism, University of Perugia, Perugia, Italy;
- * Diabetes Research Unit, Cardiff University Medical School, Llandough Hospital, Penarth Wales, UK
Abstract
Objective. To compare pharmacokinetics and -dynamics (PD) of insulin glargine (GLA) and detemir (DET), 24 subjects with T1DM (38±10 years, BMI 22.4±1.6, kg/m2, HbA1c 7.2±0.7%, mean±SD) were studied after 2 week treatment with either GLA or DET once daily (randomized, double-blind, cross-over study).
Methods. Plasma glucose (PG) was clamped at 100 mg/dl for 24-h after s.c. injection of 0.35 U/kg. Primary endpoint was end of action (time at which PG was >150 mg/dl).
Results. With GLA, PG remained at 103±3.6 mg/dl up to 24 h (all subjects completed the study). PG increased progressively after 16 h with DET, and only 8 subjects (33%) completed the study with PG <180 mg/dl. Glucose infusion rate (GIR) was similar with DET and GLA for 12 h, after which it decreased more rapidly with DET (p<0.001). Estimated total insulin activity (GIR-AUC0-end of GIR) was 1412±662 and 915±225 mg/Kg (GLA vs DET, p<0.05), with median time of end of action 24 h and 17.5 h (GLA and DET, p<0.001). Antilipolytic action of DET was lower than that of GLA (AUC free fatty acids0-24 =11±1.7 vs 8±2.8 mmol/l, respectively, p<0.001).
Conclusions. DET has effects similar to GLA during initial 12 h, but lower during 12-24 h.
Footnotes
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- Received January 1, 2007.
- Accepted July 4, 2007.
- Copyright © American Diabetes Association
