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

  1. Francesca Porcellati, MD1,
  2. Paolo Rossetti, MD1,
  3. Natalia Ricci Busciantella, MD1,
  4. Stefania Marzotti, MD1,
  5. Paola Lucidi, MD1,
  6. Steven Luzio, MD2,
  7. David R. Owens, MD2,
  8. Geremia B. Bolli, MD1 and
  9. Carmine G. Fanelli, MD1
  1. 1Department of Internal Medicine, Section of Internal Medicine, Endocrinology and Metabolism, University of Perugia, Perugia, Italy
  2. 2Diabetes Research Unit, Cardiff University Medical School, Llandough Hospital, Penarth Wales, U.K
  1. Address correspondence and reprint requests to Prof. Geremia B. Bolli, Internal Medicine, Endocrinology and Metabolism, University of Perugia, Via E. Dal Pozzo, 06126 Perugia, Italy. E-mail: gbolli{at}unipg.it

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.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 10 July 2007. DOI: 10.2337/dc07-0002.

    Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/dc07-0002.

    G.B.B. has received honoraria for scientific advising and consulting from sanofi-aventis, NovoNordisk, and Eli Lilly and Co.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted July 4, 2007.
    • Received January 1, 2007.
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  1. Published online before print July 10, 2007, doi: 10.2337/dc07-0002 Diabetes Care October 2007 vol. 30 no. 10 2447-2452
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