Effects of the Long-Acting Human Glucagon-Like Peptide-1 Analog Liraglutide on β-Cell Function in Normal Living Conditions
- Andrea Mari, PHD1,
- Kristine Degn, MD, PHD2,
- Birgitte Brock, MD, PHD2,
- Joergen Rungby, MD, DMSC2,
- Ele Ferrannini, MD3 and
- Ole Schmitz, MD, DMSC2
- 1National Research Council Institute of Biomedical Engineering, Padua, Italy
- 2Department of Endocrinology and Diabetes, University Hospital, University of Aarhus, Aarhus, Denmark
- 3National Research Council Institute of Clinical Physiology, University of Pisa, Pisa, Italy
- Address correspondence and reprint requests to Andrea Mari, Institute of Biomedical Engineering-CNR, Corso Stati Uniti 4, 35127 Padova, Italy. E-mail: andrea.mari{at}isib.cnr.it
Liraglutide is a long-acting glucagon-like peptide (GLP)-1 analog, which exerts its glucose-lowering action through multiple mechanisms (1). One important feature of liraglutide is its ability to enhance β-cell function. The effects on β-cell function have been demonstrated using standardized β-cell function tests based on intravenous glucose administration (2–4). However, these studies may not reflect the modes of action of liraglutide during normal living. To assess the effects of liraglutide on β-cell function in normal living, we have used a validated β-cell model to analyze 24-h triple-meal experiments.
RESEARCH DESIGN AND METHODS—
This study includes data used for a different analysis in a previous publication (3), where the experimental protocol, approved by the local ethics committee and performed in accordance with the Helsinki Declaration, was described in detail.
Thirteen type 2 diabetic patients (five women and eight men) were examined. Their mean ± SD age was 56.4 ± 9.2 years, BMI was 31.2 ± 3.6 kg/m2, last measured A1C before inclusion was 7.3 ± 0.4% (normal range <6.4%), and the duration of diabetes was 3.0 ± 2.6 years.
The study is a randomized, double-blind, placebo-controlled, crossover trial, with a washout period of 6–7 weeks between treatments. After inclusion, the patients discontinued their oral hypoglycemic agents (sulfonylurea and metformin) for 2 weeks before the study. Liraglutide (6 μg/kg body wt) or placebo was injected subcutaneously into the abdomen once daily (at ∼0745 h) for 9 days. After 7 days of treatment, the patients where hospitalized at 2200 h. On the next day, while continuing treatment, three standard meals were served at 0800, 1200, …
