Inhibition of Dipeptidyl Peptidase IV Improves Metabolic Control Over a 4-Week Study Period in Type 2 Diabetes
Inhibition of Dipeptidyl Peptidase IV Improves Metabolic Control Over a 4-Week Study Period in Type 2 Diabetes Bo Ahrén , MD, PHD 1 2 , Erik Simonsson , MD 1 , Hillevi Larsson , MD, PHD 1 , Mona Landin-Olsson , MD, PHD 2 , Hlin Torgeirsson , MD 2 , Per-Anders Jansson , MD, PHD 3 , Madeléne Sandqvist...
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Published in | Diabetes care Vol. 25; no. 5; pp. 869 - 875 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Alexandria, VA
American Diabetes Association
01.05.2002
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Subjects | |
Online Access | Get full text |
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Summary: | Inhibition of Dipeptidyl Peptidase IV Improves Metabolic Control Over a 4-Week Study Period in Type 2 Diabetes
Bo Ahrén , MD, PHD 1 2 ,
Erik Simonsson , MD 1 ,
Hillevi Larsson , MD, PHD 1 ,
Mona Landin-Olsson , MD, PHD 2 ,
Hlin Torgeirsson , MD 2 ,
Per-Anders Jansson , MD, PHD 3 ,
Madeléne Sandqvist , MD 3 ,
Peter Båvenholm , MD, PHD 4 ,
Suad Efendic , MD, PHD 4 ,
Jan W. Eriksson , MD, PHD 5 ,
Sheila Dickinson , MSC 6 and
David Holmes , MD 6
1 Department of Medicine, Lund University, Malmö, Sweden
2 Department of Medicine, Lund University, Lund, Sweden
3 Department of Medicine, Göteborg University, Göteborg, Sweden
4 Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden
5 Department of Medicine, Umeå University, Umeå, Sweden
6 Novartis, Basel, Switzerland
Abstract
OBJECTIVE —Glucagon-like peptide-1 (GLP-1) has been proposed as a new treatment modality for type 2 diabetes. To circumvent the drawback
of the short half-life of GLP-1, inhibitors of the GLP-1–degrading enzyme dipeptidyl peptidase IV (DPP IV) have been examined.
Such inhibitors improve glucose tolerance in insulin-resistant rats and mice. In this study, we examined the 4-week effect
of 1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP DPP728), a selective, orally active
inhibitor of DPP IV, in subjects with diet-controlled type 2 diabetes in a placebo-controlled double-blind multicenter study.
RESEARCH DESIGN AND METHODS —A total of 93 patients (61 men and 32 women), aged 64 ± 9 years (means ± SD) and with BMI 27.3 ± 2.7 kg/m 2 , entered the study. Fasting blood glucose was 8.5 ± 1.5 mmol/l, and HbA 1c was 7.4 ± 0.7%. Before and after treatment with NVP DPP728 at 100 mg × 3 ( n = 31) or 150 mg × 5 ( n = 32) or placebo ( n = 30), subjects underwent a 24-h study with standardized meals (total 2,000 kcal).
RESULTS —Compared with placebo, NVP DPP728 at 100 mg t.i.d. reduced fasting glucose by 1.0 mmol/l (mean), prandial glucose excursions
by 1.2 mmol/l, and mean 24-h glucose levels by 1.0 mmol/l (all P < 0.001). Similar reductions were seen in the 150-mg b.i.d. treatment group. Mean 24-h insulin was reduced by 26 pmol/l in
both groups ( P = 0.017 and P = 0.023). Although not an efficacy parameter foreseen in the study protocol, HbA 1c was reduced to 6.9 ± 0.7% in the combined active treatment groups ( P < 0.001). Laboratory safety and tolerability was good in all groups.
CONCLUSIONS —We conclude that inhibition of DPP IV is a feasible approach to the treatment of type 2 diabetes in the early stage of the
disease.
DDP IV, dipeptidyl peptidase IV
FPG, fasting plasma glucose
GIP, gastric inhibitory polypeptide
GLP-1, glucagon-like peptide-1
NVP DPP728, 1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine
Footnotes
Address correspondence and reprint requests to Dr. Bo Ahrén, Department of Medicine, Lund University, B11 BMC, S-221 84 Lund,
Sweden. E-mail: bo.ahren{at}med.lu.se .
Received for publication 15 August 2001 and accepted in revised form 5 February 2002.
Bo Ahrén, Peter Båvenholm, Suad Efendic, Per-Anders Jansson, Madeléne Sandqvist, and Erik Simonsson have received grant support
and Jan W. Eriksson has received consulting fees from Novartis, Basel, Switzerland.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 ObjectType-News-3 content type line 23 |
ISSN: | 0149-5992 1935-5548 1935-5548 |
DOI: | 10.2337/diacare.25.5.869 |