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Comparison of pharmacokinetics and dynamics of the long acting insulin analogues glargine and detemir at steady state in type 1 diabetes: a double-blind, randomised, cross-over study

Porcellati, Francesca, Rossetti, Paolo, Ricci Busciantella, Natalia, Marzotti, Stefania, Lucidi, Paola, Luzio, Stephen Denis, Owens, David Raymond, Bolli, Geremia B. and Fanelli, Carmine G. 2007. Comparison of pharmacokinetics and dynamics of the long acting insulin analogues glargine and detemir at steady state in type 1 diabetes: a double-blind, randomised, cross-over study. Diabetes care 30 (10) , pp. 2447-2452. 10.2337/dc07-0002

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Abstract

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). RESEARCH DESIGN AND 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 acids0–24 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. Abbreviations: AUC, area under the curve • FFA, free fatty acid • GIR, glucose infusion rate • IIR, intravenous insulin infusion rate • IV, intravenous • SC, subcutaneous

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Diabetes Association
ISSN: 01495992
Last Modified: 04 Jun 2017 01:32
URI: http://orca.cf.ac.uk/id/eprint/411

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