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

Ahrén, Bo LU ; Simonsson, Erik; Larsson, Hillevi; Landin-Olsson, Mona LU ; Torgeirsson, Hlin; Jansson, Per-Anders; Sandqvist, Madeléne; Båvenholm, Peter; Efendic, Suad and Eriksson, Jan W, et al. (2002) In Diabetes Care 25(5). 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... (More)
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. (Less)
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Contribution to journal
publication status
published
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Diabetes Care
volume
25
issue
5
pages
869 - 875
publisher
American Diabetes Association
external identifiers
  • pmid:11978683
  • wos:000183491300011
  • scopus:0036583164
ISSN
1935-5548
DOI
10.2337/diacare.25.5.869
language
English
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yes
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596fb5df-8444-431a-9e06-5e532b4baf20 (old id 107861)
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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11978683&dopt=Abstract
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2007-06-27 08:39:13
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2017-10-01 04:51:43
@article{596fb5df-8444-431a-9e06-5e532b4baf20,
  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 &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, HbA(1c) 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.},
  author       = {Ahrén, Bo and Simonsson, Erik and Larsson, Hillevi and Landin-Olsson, Mona and Torgeirsson, Hlin and Jansson, Per-Anders and Sandqvist, Madeléne and Båvenholm, Peter and Efendic, Suad and Eriksson, Jan W and Dickinson, Sheila and Holmes, David},
  issn         = {1935-5548},
  language     = {eng},
  number       = {5},
  pages        = {869--875},
  publisher    = {American Diabetes Association},
  series       = {Diabetes Care},
  title        = {Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes.},
  url          = {http://dx.doi.org/10.2337/diacare.25.5.869},
  volume       = {25},
  year         = {2002},
}