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.
  
  
  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.
authors.affiliation: Department of Medicine, Lund University, Malmö, Sweden. bo.ahren@med.lu.se
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
authors.forename: Erik
authors.initials: E
authors.lastname: Simonsson
authors.forename: Hillevi
authors.initials: H
authors.lastname: Larsson
authors.forename: Mona
authors.initials: M
authors.lastname: Landin-Olsson
authors.forename: Hlin
authors.initials: H
authors.lastname: Torgeirsson
authors.forename: Per-Anders
authors.initials: PA
authors.lastname: Jansson
authors.forename: Madeléne
authors.initials: M
authors.lastname: Sandqvist
authors.forename: Peter
authors.initials: P
authors.lastname: Båvenholm
authors.forename: Suad
authors.initials: S
authors.lastname: Efendic
authors.forename: Jan W
authors.initials: JW
authors.lastname: Eriksson
authors.forename: Sheila
authors.initials: S
authors.lastname: Dickinson
authors.forename: David
authors.initials: D
authors.lastname: Holmes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D018819:Dipeptidyl Peptidase 4; D006442:Glycated Hemoglobin; D007328:Insulin; D009570:Nitriles; D011759:Pyrrolidines; C121834:1-(((2-((5-cyanopyridin-2-yl)amino)ethyl)amino)acetyl)-2-cyano-(S)-pyrrolidine