Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes.

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@article{596fb5df8444431a9e065e532b4baf20,
title = "Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes.",
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 x 3 (n = 31) or 150 mg x 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.",
author = "Bo Ahr{\'e}n and Erik Simonsson and Hillevi Larsson and Mona Landin-Olsson and Hlin Torgeirsson and Per-Anders Jansson and Madel{\'e}ne Sandqvist and Peter B{\aa}venholm and Suad Efendic and Eriksson, {Jan W} and Sheila Dickinson and David Holmes",
year = "2002",
doi = "10.2337/diacare.25.5.869",
language = "English",
volume = "25",
pages = "869--875",
journal = "Diabetes Reviews",
issn = "1935-5548",
publisher = "American Diabetes Association",
number = "5",

}