Dipeptidyl peptidase IV inhibitors: how do they work as new antidiabetic agents?

@article{Mcintosh2005DipeptidylPI,
  title={Dipeptidyl peptidase IV inhibitors: how do they work as new antidiabetic agents?},
  author={Christopher H. S. Mcintosh and Hans-Ulrich Demuth and John Andrew Pospisilik and Raymond A. Pederson},
  journal={Regulatory Peptides},
  year={2005},
  volume={128},
  pages={159-165}
}
Applications of dipeptidyl peptidase IV inhibitors in diabetes mellitus.
Dipeptidyl peptidase 4 inhibition and vildagliptin therapy for type 2 diabetes.
TLDR
The results suggest that vildagliptin, as a member of the novel class of DPP-4 inhibitors, has the potential to significantly change the clinical management of diabetes.
Dipeptidyl peptidase 4 inhibition and vildagliptin therapy for type 2 diabetes
  • S. Del Prato
  • Medicine, Biology
    International journal of clinical practice. Supplement
  • 2007
TLDR
Results suggest that vildagliptin, as a member of the novel class of DPP‐4 inhibitors, has the potential to significantly change the clinical management of diabetes.
Dipeptidyl peptidase IV inhibition alters the hemodynamic response to angiotensin-converting enzyme inhibition in humans with the metabolic syndrome.
TLDR
Because a high percentage of type 2 diabetics have the metabolic syndrome, the effects of DPP-4 inhibition in such patients are of particular importance, and because metabolic syndrome patients are nearly always subjected to multidrug regimens, clarifying the interactions of D PP-4 inhibitors with other medications prescribed for these patients is also a worthwhile investment.
Vildagliptin: an inhibitor of dipeptidyl peptidase-4 with antidiabetic properties
  • B. Ahrén
  • Biology, Medicine
    Expert opinion on investigational drugs
  • 2006
TLDR
In clinical trials, vildagliptin improves glycaemic control both as monotherapy and in combination with metformin for periods of ≤ 52 weeks in subjects with Type 2 diabetes, and has proven to be safe and tolerable, with a low occurrence of hypoglycaemia.
Efficacy of the dipeptidyl peptidase IV inhibitor isoleucine thiazolidide (P32/98) in fatty Zucker rats with incipient and manifest impaired glucose tolerance
TLDR
Investigation of the therapeutic effects of incretin enhancement on incipient impaired glucose tolerance and manifest IGT using the dipeptidyl peptidase IV (DPP‐4) inhibitor P32/98‐ and fatty Zucker rat (ZR, fa/fa) as a model.
Dipeptidyl Peptidase-IV: A Brief Review.
TLDR
DPP IV inhibition improves the impaired insulin secretion and decrease postprandial concentrations of glucagon by enhancing the incretin hormone levels of Glucagon like peptide-1(GLP-1) and Glucose dependent insulinotropic polypeptide (GIP).
Saxagliptin: a dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus.
  • Joshua J. Neumiller, R. Campbell
  • Medicine, Biology
    American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
  • 2010
TLDR
Saxagliptin, a DPP-4 inhibitor approved for the treatment of type 2 diabetes, demonstrated safety and efficacy in lowering HbA(1c), FPG, and PPG levels as both monotherapy and in combination with other oral antidiabetic medications.
Role of DPP IV Inhibitor in Type-2 Diabetes Mellitus
TLDR
As the insulinotropic action of GLP-1 is preserved in type 2 diabetic patients, this peptide was likely to be developed s a therapeutic agent for this disease.
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References

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Therapeutic potential of dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes
  • D. Drucker
  • Biology, Medicine
    Expert opinion on investigational drugs
  • 2003
TLDR
This review summarises the biology of incretin action, the structure, expression and pleiotropic biological activities of DPP-IV and provides an overview of the rationale, potential merits and theoretical pitfalls in the development of D PP-IV inhibitors for the treatment of type 2 diabetes.
Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes.
TLDR
It is concluded that side effects of inhibition therapy are likely to be mild, and DPP-IV inhibition may be an effective supplement to diet and exercise treatment in attempts to prevent the deterioration of glucose metabolism associated with the Western lifestyle.
Dipeptidyl peptidase IV inhibitor treatment stimulates β-cell survival and islet neogenesis in streptozotocin-induced diabetic rats
TLDR
In vitro studies using a β-(INS-1) cell line showed a dose-dependent prevention of STZ-induced apoptotic cell-death by both GIP and GLP-1, supporting a role for the incretins in eliciting the in vivo results.
Enhancing incretin action for the treatment of type 2 diabetes.
TLDR
The need for daily injections of potentially immunogenic GLP-1-derived peptides and the potential for unanticipated side effects with chronic use of DPP-IV inhibitors will require ongoing scrutiny of the risk-benefit ratio for these new therapies as they are evaluated in the clinic.
Dipeptidyl peptidase IV inhibition in animal models of diabetes.
TLDR
DP IV rapidly cleaves the N-terminal dipeptide from a number of metabolic hormones and neuroendocrine factors including NPY, PYY, and the gluco-regulatory peptides glucagonlike peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptides (GIP) and glucagon.
Inhibition of dipeptidyl peptidase IV with NVP-DPP728 increases plasma GLP-1 (7–36 amide) concentrations and improves oral glucose tolerance in obese Zucker rats
TLDR
The improvement observed in prandial glucose homeostasis during DPP-IV inhibition suggests that inhibition of this enzyme is a promising treatment for Type II diabetes.
Long-term treatment with the dipeptidyl peptidase IV inhibitor P32/98 causes sustained improvements in glucose tolerance, insulin sensitivity, hyperinsulinemia, and beta-cell glucose responsiveness in VDF (fa/fa) Zucker rats.
TLDR
Long-term DP IV inhibitor treatment was shown to cause sustained improvements in glucose tolerance, insulinemia, beta-cell glucose responsiveness, and peripheral insulin sensitivity, novel effects that provide further support for the use of DP IV inhibitors in the treatment of diabetes.
Dipeptidyl peptidase IV inhibition potentiates the insulinotropic effect of glucagon-like peptide 1 in the anesthetized pig.
TLDR
By reducing GLP-1 degradation, DPP IV inhibition potentiates the insulinotropic effect of GLP1 and may, therefore, be a viable approach to the management of diabetes.
Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes.
TLDR
In inhibition of DPP IV is a feasible approach to the treatment of type 2 diabetes in the early stage of the disease, as concluded in a placebo-controlled double-blind multicenter study.
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