In:
Diabetes Care, American Diabetes Association, Vol. 25, No. 5 ( 2002-05-01), p. 869-875
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/m2, entered the study. Fasting blood glucose was 8.5 ± 1.5 mmol/l, and HbA1c 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 & lt; 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, HbA1c was reduced to 6.9 ± 0.7% in the combined active treatment groups (P & lt; 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.
Type of Medium:
Online Resource
ISSN:
0149-5992
,
1935-5548
DOI:
10.2337/diacare.25.5.869
Language:
English
Publisher:
American Diabetes Association
Publication Date:
2002
detail.hit.zdb_id:
1490520-6
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