Abstract
Aims
To test potential efficacy of liraglutide, a GLP-1 receptor agonist, in subjects with type 1 diabetes (T1DM).
Methods
We have recruited nine T1DM patients (age 40.1 ± 6.4 years, duration of diabetes 19.2 ± 8.8 years, BMI 24.3 ± 3.5 kg/m2, HbA1c 8.2 ± 1.0 %–66 ± 11 mmol/mol, daily insulin dose: 0.6 ± 0.1 IU/kg) on continuous subcutaneous insulin therapy with undetectable C-peptide. In addition to existing treatment was administered in single-blind (a) therapy subcutaneously with 0.1 ml of saline solution for 3 days and (b) 0.1 ml of liraglutide (0.6 mg/day) for a further 3 days with daily glucose excursions recorded by continuous glucose monitoring.
Results
Adding liraglutide resulted in a significant reduction in mean blood glucose (138 ± 29 vs. 163 ± 29 mg/dl, p < 0.0001) and standard deviation (42 ± 9 vs. 60 ± 15 mg/dl, p < 0.0001). The area under the curve (AUC) for blood glucose >140 mg/dl was also significantly reduced (22.2 ± 16.4 vs. 41.1 ± 19.7 mg/dl h, p < 0.05) with no difference in AUC for blood glucose <70 mg/dl (liraglutide 0.7 ± 0.9 mg/dl h; placebo: 0.8 ± 1.4 mg/dl h, p = NS). Finally, adding liraglutide reduced daily insulin requirement (37.5 ± 17.2 vs. 42.9 ± 22.4 UI/day, p < 0.01).
Conclusions
Short-term treatment with liraglutide, in T1DM, reduces average blood glucose, blood glucose variability and daily insulin requirement without increasing risk of hypoglycemia.
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Abbreviations
- T1DM:
-
Type 1 diabetes mellitus
- AUC:
-
Area under the curve
- GLP-1 RA:
-
Glucagon-like peptide 1 receptor agonist
- CSII:
-
Continuous subcutaneous insulin therapy
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Acknowledgments
IC was supported in part by a fellowship grant from Fondazione Diabete Ricerca-MSD. The study was supported by the PRIN grant 2010 YK7Z5K_006 and grant 2010 JS3PMZ_002.
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SDP has received honoraria for advisory work and lectures from Astra Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Intarcia, Janssen, Merck Sharpe and Dohme, Novartis, Novo Nordisk, Roche Diagnostics, sanofi aventis and Takeda as well as research support from Bristol-Myers Squibb, Merck Sharpe and Dohme, Novartis and Novo Nordisk. IC, MA, SKP and GD have no conflict to declare.
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All procedures followed were in accordance with the Ethical Standards of the responsible Institutional Committee on Human Experimentation and with the Helsinki Declaration of 1975, as revised in 2008.
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Informed consent was obtained from all patients from being included in the study.
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Crisci, I., Aragona, M., Politi, K.S. et al. GLP-1 receptor agonists in type 1 diabetes: a proof-of-concept approach. Acta Diabetol 52, 1129–1133 (2015). https://doi.org/10.1007/s00592-015-0800-6
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DOI: https://doi.org/10.1007/s00592-015-0800-6