Dipeptidyl peptidase-4 inhibitors

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Inhibitors of Dipeptidyl peptidase 4 , also DPP-4 inhibitors, are a new class of oral hypoglycemics which block DPP-4.

Their mechanism of action is thought to result from increased Incretin levels (GLP-1 and GIP),^[1][2][3] which, inhibit glucagon release (which increases the blood glucose) but more importantly increase insulin secretion and decrease gastric emptying.

Drugs belonging to this class are vildagliptin^[4], sitagliptin^[5] and saxagliptin.

Although extensive long-term, pre-clinical studies of the major DPP-4 inhibitors has failed to show any evidence of potential to cause tumors in laboratory animals, there was one in-vitro (i.e., test tube) study that has raised some questions. ^[6]

References

1. ^ McIntosh CH, Demuth HU, Pospisilik JA, Pederson R. Dipeptidyl peptidase IV inhibitors: how do they work as new antidiabetic agents? Regul Pept. 2005 Jun 15;128(2):159-65. PMID:15780435 [1].
2. ^ Behme MT, Dupre J, McDonald TJ. Glucagon-like peptide 1 improved glycemic control in type 1 diabetes. BMC Endocr Disord. 2003 Apr 10;3(1):3. PMID 12697069. Full Free Text.
3. ^ Dupre J, Behme MT, Hramiak IM, McFarlane P, Williamson MP, Zabel P, McDonald TJ. Glucagon-like peptide I reduces postprandial glycemic excursions in IDDM. Diabetes. 1995 Jun;44(6):626-30. PMID 7789625.
4. ^ Banting and Best Diabetes Centre at UT laf237 - Vildagliptin
5. ^ Banting and Best Diabetes Centre at UT mk-0431 - Sitagliptin
6. ^ Masur K et al. DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells, Regul Pept. ,137 (3) p. 147-55 (2006) PMID 16908079.